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Betel quid (BQ) use disorder (BUD) is prevalent in many Asian countries, impacting approximately 600 million people. We conducted a randomized clinical trial to analyze the impact of MAOA genetic variations on the severity of BQ craving. This was measured using DSM-5 criteria and the Yale-Brown Obsessive-Compulsive Scale modified for betel quid use (Y-BOCS-BQ). Participants were grouped according to the severity of BUD and MAOA gene single-nucleotide polymorphism (SNP) rs5953210 genotypes. The Y-BOCS-BQ scores were assessed at baseline (week 0) and during follow-up at weeks 2, 4, 6, and 8. The AA genotype group showed significantly greater reductions in Y-BOCS-BQ at weeks 2 (p = 0.0194), 4 (p = 0.0078), 6 (p = 0.0277), and 8 (p = 0.0376) compared to the GG genotype group. Additionally, within the antidepressant group, the AA genotype showed significant reductions in the Y-BOCS-BQ scores at weeks 2 (p = 0.0313), 4 (p = 0.0134), 6 (p = 0.0061), and 8 (p = 0.0241) compared to the GG genotype. The statistical analysis revealed a significant interaction between the treatment and placebo groups based on MAOA genotypes, with the AA genotype in the treatment group exhibiting a more pronounced decrease in Y-BOCS-BQ score (p interaction <0.05) at week 6. Our study highlights the importance of considering genetic factors when developing personalized treatment plans for BUD.
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Antidepresivos , Areca , Ansia , Monoaminooxidasa , Polimorfismo de Nucleótido Simple , Humanos , Monoaminooxidasa/genética , Masculino , Femenino , Adulto , Areca/efectos adversos , Antidepresivos/uso terapéutico , Ansia/efectos de los fármacos , Trastornos Relacionados con Sustancias/genética , Genotipo , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
Background and Objective: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme involved in folate metabolism and one-carbon metabolism. MTHFR gene polymorphism affects enzyme activity. MTHFR gene polymorphism is closely related to many human diseases, such as cardiocerebrovascular diseases, diabetes, neural tube defects (NTDs), tumors, and so on. In the field of Andrology, MTHFR gene polymorphism may be associated with male infertility and erectile dysfunction (ED), and there is a possibility of treating male infertility and ED by supplementing with folic acid. However, its exact pathophysiologic mechanism is not fully understood. We sought to obtain a robust understanding of the interactions between MTHFR gene polymorphism, oxidative stress, DNA methylation, hyperhomocysteinemia (HHcy), male infertility, and ED. Methods: We performed a non-systematic literature review using the PubMed database to identify articles specifically related to MTHFR, male infertility and ED. Key Content and Findings: Our literature review on MTHFR gene polymorphism in male infertility patients indicates a significant association between C677T gene polymorphism and male infertility. There is limited literature on the correlation between ED and MTHFR gene polymorphism, and there are two different conclusions, related and unrelated. More clinical data are needed to clarify the conclusion. There is a possibility of using folic acid supplementation to treat male infertility and ED, especially for patients with thymine-thymine (TT) genotype. Future research is necessary to further understand the relationship between MTHFR gene polymorphism and male infertility and ED. Conclusions: Our literature review on MTHFR gene polymorphism in male infertility patients indicates a significant association between C677T gene polymorphism and male infertility. Folic acid supplementation can improve sperm quality. The correlation between MTHFR gene polymorphisms and ED is questionable and needs to be confirmed by more clinical data. MTHFR gene polymorphisms are associated with homocysteine (Hcy) levels, which affects vascular endothelial function and may be related to the development of vascular ED (VED). Folic acid supplementation improves International Index for Erectile Function (IIEF) questionnaire scores in ED patients in whom phosphodiesterase 5 inhibitor (PDE5i) alone is ineffective.
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PD-1 has a noteworthy function in developing acute myeloid leukemia (AML). The expression of PD-1 on effector T cells is regulated at the protein level depending on the interactions between cells. The objective of the study was to evaluate the PD-1 concentration levels and the polymorphism genetic variants (rs36084323 G/A) in Iraqi Arab patients with AML. Sanger's DNA sequencing was used, and the assessments were done by enzyme-linked immunosorbent assay and PD-1 gene polymorphism SNP rs36084323 G/A. The frequency of rs36084323 was significantly different between AML and control, with a lower risk for AML seen in patients with GA genotype (odds ratio; 95% confidence interval: 0.53; 0.32-0.87). PD-1 elevated AML compared to control (213.1 pg/mL vs. 178.8 pg/mL). in AML patients, there is upregulation in PD-1, which indicates that PD-1 is a possible biomarker for AML. PD-1 rs36084323 G/A may have a role in AML risk.
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Dairy products, a major source of calcium, demonstrate a number of beneficial effects, not only protecting against the development of osteoporosis (OP) but also suppressing the onset of type-2 diabetes (T2DM) and improving bone mineral density (BMD). Dairy consumption is closely linked to lactose tolerance. One of the genetic factors predisposing individuals to lactose intolerance is rs4988235 polymorphism of the MCM6 gene. The aim of this reported study was to analyse the relationship between the rs4988235 variant of the MCM6 gene and bone mineral density and the risk of type-2 diabetes in women after menopause. METHODS: The study was conducted among 607 female patients in the postmenopausal period in whom bone densitometry and vitamin-D3 levels were assayed and genotyping of the rs4988235 polymorphism of MCM6 gene was performed. The obtained results were analysed for the presence of T2DM, obesity surrogates, medical data, and past medical history. RESULTS: The distribution of genotype frequencies was consistent with the Hardy-Weinberg equilibrium (p > 0.050). Postmenopausal women with the GG homozygote of rs4988235 polymorphism consumed significantly less calcium (dairy), which was probably related to the observed lactose intolerance. The GG homozygote of women with rs4988235 polymorphism was significantly more likely to have T2DM relative to the A allele carriers (p = 0.023). GG homozygotes had significantly lower femoral-vertebral mineral density despite the significantly more frequent supplementation with calcium preparations (p = 0.010), vitamin D (p = 0.01), and anti-osteoporotic drugs (p = 0.040). The obtained results indicate a stronger loss of femoral-neck mineral density with age in the GG homozygotes relative to the A allele carriers (p = 0.038). CONCLUSIONS: In the population of women after menopause, the carriage of the G allele of rs4988235 polymorphism of the MCM6 gene, i.e., among the patients with lactose intolerance, significantly increased the risk of developing T2DM and the loss of BMD.
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Densidad Ósea , Diabetes Mellitus Tipo 2 , Intolerancia a la Lactosa , Componente 6 del Complejo de Mantenimiento de Minicromosoma , Polimorfismo de Nucleótido Simple , Posmenopausia , Humanos , Femenino , Intolerancia a la Lactosa/genética , Densidad Ósea/genética , Persona de Mediana Edad , Posmenopausia/genética , Diabetes Mellitus Tipo 2/genética , Componente 6 del Complejo de Mantenimiento de Minicromosoma/genética , Anciano , Factores de Riesgo , Predisposición Genética a la Enfermedad , Genotipo , Productos Lácteos , Calcio de la Dieta/administración & dosificaciónRESUMEN
Diabetic kidney disease (DKD) is a common microvascular complication of diabetes, whose complex etiology involves a genetic component. Growth arrest-specific 5 (GAS5), a long noncoding RNA (lncRNA) gene, has been recently shown to regulate renal fibrosis. Here, we aimed to explore the potential role of GAS5 gene polymorphisms in the predisposition to DKD. One single-nucleotide (rs55829688) and one insertion/deletion polymorphism (rs145204276) of GAS5 gene were surveyed in 778 DKD cases and 788 DKD-free diabetic controls. We demonstrated that diabetic subjects who are heterozygous at rs55829688 (TC; AOR, 1.737; 95% CI, 1.028-2.937; p=0.039) are more susceptible to advanced DKD but not early-staged DKD, as compared to diabetic subjects who are homozygous for the major allele of rs55829688 (TT). Carriers of at least one minor allele (C) of rs55829688 (TC and CC; AOR, 1.317; 95% CI, 1.023-1.696; p=0.033) more frequently suffer from advanced DKD than do those homozygotes for the major allele (TT). Furthermore, in comparison to those who do not carry the minor allele of rs55829688 (TT), advanced DKD patients possessing at least one minor allele of rs55829688 (TC and CC) exhibited a lower glomerular filtration rate, revealing an impact of rs55829688 on renal co-morbidities of diabetes. In conclusion, our data indicate an association of GAS5 gene polymorphisms with the progression of DKD.
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Nefropatías Diabéticas , Progresión de la Enfermedad , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/patología , Masculino , Persona de Mediana Edad , Femenino , Anciano , Estudios de Casos y Controles , Alelos , Adulto , Estudios de Asociación GenéticaRESUMEN
This study explores the association of vitamin D-binding protein (VDBP) gene polymorphisms, vitamin D levels, and the severity of COVID-19, including the need for intensive care unit (ICU) hospitalization. We analyzed a cohort of 56 consecutive age- and gender-matched adult COVID-19-positive patients and categorized them into three groups: outpatients with mild illness, inpatients with moderate disease, and ICU patients. We measured levels of free, total, and bioavailable 25-hydroxyvitamin D [25(OH)D], VDBP, and albumin. VDBP polymorphisms rs5488 and rs7041 were identified using real-time PCR. A significant proportion of ICU patients were vitamin D-deficient (56.25%) compared to outpatients (10%) and inpatients (5%) (p = 0.0003). ICU patients also had notably lower levels of VDBP (median: 222 mg/L) and total 25(OH)D (median: 18.8 ng/mL). Most patients carried heterozygous rs7041 (60.7%) and wild-type rs4588 (58.9%) genotypes. The distribution of rs7041 SNP varied significantly among groups (p = 0.0301), while rs4588 SNP distribution did not (p = 0.424). Heterozygous rs4588 patients had significantly lower VDBP levels (p = 0.029) and reduced bioavailable 25(OH)D compared to those with wild-type rs4588 (p = 0.020). Our findings indicate that VDBP gene polymorphisms, particularly rs7041 and rs4588, are associated with vitamin D status and the severity of COVID-19. The lower VDBP levels and bioavailable vitamin D in ICU patients suggest that these genetic variants may influence disease severity and hospitalization needs. These results highlight the potential role of VDBP polymorphisms in COVID-19 severity, suggesting that genetic screening could be valuable in assessing the risk of severe outcomes and guiding personalized treatment strategies.
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Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that impacts women before reaching menopause. In addition to notable features (irregular ovulation, elevated androgen levels, and the existence of numerous ovarian cysts), individuals with PCOS frequently encounter diverse metabolic, cardiovascular, and psychological conditions. The onset of PCOS is influenced by a combination of factors, and various genetic variations are believed to play a significant role in its progression. The objective of the current study was to explore the link between genetic variations in the candidate genes thyroid-adenoma-associated (THADA) gene and insulin receptor (INSR) and susceptibility to developing PCOS. We conducted an extensive search across various databases, including Google Scholar, PubMed, Science Direct, Scopus, and EMBASE, to compile relevant case-control studies and literature reviews for subsequent statistical analysis. In the present study, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was followed, a guideline for Systematic Reviews and Meta-Analysis. While a previous meta-analysis explored the correlation between INSR rs1799817 and THADA rs13429458 and their association with susceptibility to PCOS, our current study did not integrate any findings from these prior investigations. Our research encompassed articles published between 2017 and 2023, and we employed MetaGenyo software to assess the collected data. Statistical power analysis was performed using G*Power 3.1 software. Odds ratios and their corresponding 95% confidence intervals were calculated for each genetic model. Fifteen studies that met the criteria were analyzed. Out of these, ten studies, involving 1,189 cases and 1,005 controls, examined the INSR rs1799817 gene polymorphism, while five studies, including 783 cases and 553 controls, investigated the THADA rs13429458 gene polymorphism. The meta-analysis results indicated that there was no statistically significant association between the INSR rs1799817 gene polymorphism and the risk of PCOS (p>0.05). In contrast, the THADA rs13429458 gene polymorphism showed a significant association with PCOS risk under the over-dominant model (p<0.05). The present meta-analysis demonstrated a notable association between the THADA rs13429458 gene polymorphism and the likelihood of developing PCOS. Further rigorous studies with expanded sample sizes and diverse ethnic representation will be important to comprehensively evaluate and validate these findings.
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BACKGROUND: Intra-detrusor injection of botulinum neurotoxin type A (BoNT/A) is recommended as a possible treatment for patients with overactive bladder (OAB) in whom first-line therapies have failed. The c.190T > C (rs4994) polymorphism in the gene encoding the beta-3 adrenergic receptor (ADRB3) has been suggested to be associated with predisposition to OAB or with response to OAB treatment via a cholinergic muscarinic receptor antagonist. This prospective study aimed to use a urodynamic parameter-based assessment of response, six months after a single intra-detrusor injection of BoNT/A in female OAB patients, to elucidate possible association with the ADRB3 polymorphism. METHODS: The study group consisted of 138 consecutive, Polish, adult, female OAB patients. Urodynamic parameters were recorded before injection of BoNT/A and at six months after administration. ADRB3:rs4994 variants were identified by the sequencing of genomic DNA extracted from buccal swabs. RESULTS: Apart from baseline, and relative, increase in Maximum Cystometric Capacity (MCC) six months after BoNT/A injection, no significant differences were found in urodynamic parameters between reference TT homozygotes and women with at least one C allele. CONCLUSIONS: Our results do not exclude that ADRB3:rs4994 variants are associated with a positive urodynamic test-based response to intra-detrusor injection of BoNT/A in females with OAB.
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Fucosyltransferase 2 (FUT2) gene, which regulates the formation of Histoblood group antigens, could determine the human susceptibility to norovirus. This study aimed to investigate the correlation between FUT2 gene polymorphism and susceptibility to norovirus gastroenteritis in Han Chinese population. A total of 212 children patients with acute gastroenteritis were enrolled. The stool and serum samples were collected respectively. We used the qPCR method to detect the norovirus infection status from the stool samples, and we used serum samples to detect the FUT2 polymorphism. A case-control study was conducted to investigate the three common SNPs polymorphisms (rs281377, rs1047781, and rs601338) of FUT2 gene with sanger sequencing method. The results indicated that the homozygous genotypes and mutant allele of rs1047781 (A385T) would downgrade the risk of norovirus gastroenteritis in Chinese Han population (AA vs. TT, odds ratio [OR] = 0.098, 95% confidence interval [CI] = 0.026-0.370, p = 0.001; AA + AT vs. TT, OR = 0.118. 95% CI = 0.033-0.424, p = 0.001; A vs. T, OR = 0.528, 95% CI = 0.351-0.974, p = 0.002). There were no significant difference of rs281377 (C357T) and rs601338 (G428A) polymorphisms between norovirus positive and norovirus negative groups (p > 0.05). The haplotype T-T-G was less susceptible (OR = 0.49, 95% CI = 0.31-0.79, p = 0.0034) to norovirus infection compared to other haplotypes. Our results investigated the relationship between the FUT2 gene polymorphisms and norovirus susceptibility in Han Chinese population, and firstly revealed that children with homozygous genotypes and mutant alleles of FUT2 rs1047781 (A385T) were less susceptible to norovirus gastroenteritis.
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Pueblo Asiatico , Infecciones por Caliciviridae , Fucosiltransferasas , Galactósido 2-alfa-L-Fucosiltransferasa , Gastroenteritis , Predisposición Genética a la Enfermedad , Genotipo , Norovirus , Polimorfismo de Nucleótido Simple , Humanos , Fucosiltransferasas/genética , Infecciones por Caliciviridae/genética , Infecciones por Caliciviridae/virología , Infecciones por Caliciviridae/epidemiología , Femenino , Masculino , Gastroenteritis/virología , Gastroenteritis/genética , Estudios de Casos y Controles , Preescolar , Norovirus/genética , Pueblo Asiatico/genética , Lactante , China/epidemiología , Niño , Heces/virología , Alelos , Haplotipos , Pueblos del Este de AsiaRESUMEN
OBJECTIVE: To explore the relationship between rs1410996 polymorphism of CFH gene and essential hypertension (EH) in the Yunnan Han population. METHODS: rs1410996 of CFH gene was genotyped based on the collected clinical phenotypes of the EH patients (n = 520) and healthy people (n = 494). RESULTS: On the genotype model and dominance model, there was no relationship between rs1410996 of CFH gene and EH after adjustment (P > 0.05). On the dominance model of male EH patients, the pulse pressure (PP) level of CC genotype carriers was higher than that of (CT + TT) genotype carriers after adjustment (P < 0.05). CONCLUSION: rs1410996 of CFH gene has no correlation with the genetic susceptibility to EH in the Yunnan Han population, but it is related to the PP level in male patients.
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Pueblo Asiatico , Factor H de Complemento , Hipertensión Esencial , Predisposición Genética a la Enfermedad , Genotipo , Polimorfismo de Nucleótido Simple , Humanos , Masculino , Hipertensión Esencial/genética , Persona de Mediana Edad , Femenino , China , Factor H de Complemento/genética , Polimorfismo de Nucleótido Simple/genética , Pueblo Asiatico/genética , Frecuencia de los Genes/genética , Anciano , Estudios de Casos y Controles , Adulto , Hipertensión/genética , Estudios de Asociación Genética/métodos , Alelos , Presión Sanguínea/genéticaRESUMEN
Background: Circadian rhythms impact metabolism and the therapeutic effects of drugs. The purpose of this study was to determine the association between PER and CRY polymorphisms and caffeine citrate treatment response in infants with apnea of prematurity. Methods: A total of 221 preterm infants of gestational age <34 weeks were included in this study (160 in the response group and 61 in the non-response group). The propensity score matching method was used to perform a 1:1 matching for all premature infants, and the general characteristics and clinical outcomes of the two groups were compared. The association between polymorphisms of the circadian transcription repressors PER and CRY and caffeine citrate treatment response in infants with apnea of prematurity was analyzed with co-dominant, dominant, recessive, and over-dominant models, as well as analysis of alleles. Generalized multifactor dimensionality reduction (GMDR) analysis was used to analyze the interaction between the PER and CRY genes. Results: After propensity score matching, 45 preterm infants were included in each of the response and non-response groups, and there were no statistically significant differences in general characteristics between the two groups (P > 0.05). Infants in the non-response groups had a higher incidence of moderate and severe bronchopulmonary dysplasia (BPD) (P = 0.043), retinopathy of prematurity (ROP) (P = 0.035), and invasive ventilation (P = 0.027), and their duration of oxygen use (P = 0.041) was longer. When corrected for false discovery rate, the PER3 rs228669 recessive model (P FDR = 0.045) and the over-dominant model (P FDR = 0.045) were both associated with caffeine citrate treatment response. Preterm infants with the rs228669 CC genotype had a significantly lower rate of caffeine citrate non-response in the recessive model (OR = 0.28, 95% CI = 0.12-0.66), which was significantly higher in preterm infants with the CT genotype in the over-dominant model (OR = 4.18, 95% CI = 1.64-10.66). GMDR analysis revealed an interaction between the PER and CRY genes (P < 0.05). Conclusions: Circadian rhythms may play a role in the response of premature infants to caffeine citrate, and polymorphisms of the PER and CRY genes may influence the effectiveness of caffeine citrate treatment for apnea of prematurity.
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Objective: To investigate the association between single nucleotide polymorphisms (SNPs) of tryptophan hydroxylase 2 (TPH2) (rs11178997, rs11178998, and rs120074175) and negative life events in adolescent depression with Non-suicidal self-injury (NSSI). Methods: Genomic DNA was extracted from 197 adolescents with depression (participants group, including NSSI group and non-NSSI group), as well as from 100 healthy controls (control group), in northern China. PCR technology was utilized to amplify DNA fragments and detect genotypes in both groups. The Adolescent Life Event Scale (ASLEC) was employed to conduct a questionnaire survey among the participants and control groups. Differences in allele and genotype frequency distribution between the two groups were analyzed using the X^2 test, while generalized multifactor dimensionality reduction (GMDR) was used to analyze gene-environment interactions. Results: Significant differences were observed in ASLEC scores between the control group and both the NSSI group and non-NSSI group (P<0.05). Additionally, significant differences were found in the interpersonal relationship factor and punishment factor between the NSSI group and non-NSSI group (P < 0.05). Moreover, a significant difference was identified in SNP genotype of rs11178997 between the depression group (NSSI group + non-NSSI group) and control group (P<0.05). GMDR analysis revealed an interaction among rs11178997, rs11178998, and ASLEC. Conclusion: Adolescents with depression, particularly females, may exhibit a tendency to employ NSSI as an emotional coping mechanism when confronted with greater family and interpersonal challenges. The AT genotype of TPH2 gene locus rs11178997 is more prevalent among adolescents with depression. Furthermore, the occurrence of NSSI may be associated with an interaction involving polymorphic sites rs11178997 and rs11178998 along with life events.
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OBJECTIVES: Osteoarthritis (OA) is a complex multifactorial disease. The association of knee OA risk with ACE gene rs4343 polymorphism, gene environment synergistic effect, and angiotensin II serum level has not been previously examined. Therefore, we investigate the ACE gene rs4343 polymorphism in knee OA, and its association with severity of knee OA, and angiotensin II serum level. METHODS: Using a case-control design, we recruited 200 subjects (100 cases and 100 controls) and all were subjected to genotyping of rs4343 SNP by real-time polymerase chain reaction and assay of serum angiotensin II level by ELISA. RESULTS: G containing genotypes (AG and GG) and G allele frequencies of the ACE rs4343 polymorphism were significantly higher in the case group than that in the control group. There was significant association between ACE rs4343 genotypes and risk of knee OA under the following genetic inheritance models: GG vs. AA (P=0.003), AA vs. GG/AG (P=0.014), AG/AA vs. GG (P=0.037), and G vs. A (P<0.001). Stratified analyses showed ACE rs4343 polymorphism was evidently associated with a significantly increased risk of knee OA among those had BMI≥25% (adjusted OR=3.016; 95% CI 1.052-8.648; P=0.040). Additionally, knee OA patients with GG genotype had greater knee specific WOMAC index, Kellgren score, and serum angiotensin II level than those with AA or GA genotypes. CONCLUSION: The investigated polymorphism in the ACE gene rs4343 may reflect the risk and severity of knee OA in the Egyptian population, particularly with the GG genotype. The interaction between ACE gene rs4343 polymorphism and obesity further increased the risk of knee OA. Moreover, the higher angiotensin II level may be involved in the pathogenesis of knee OA.
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Angiotensina II , Predisposición Genética a la Enfermedad , Osteoartritis de la Rodilla , Peptidil-Dipeptidasa A , Polimorfismo de Nucleótido Simple , Humanos , Osteoartritis de la Rodilla/genética , Peptidil-Dipeptidasa A/genética , Peptidil-Dipeptidasa A/sangre , Masculino , Femenino , Angiotensina II/sangre , Estudios de Casos y Controles , Persona de Mediana Edad , Anciano , Interacción Gen-AmbienteRESUMEN
Neonatal sepsis is a common and severe infectious disease with a high mortality rate. Its pathogenesis is complex, lacks specific manifestations, and has a low positive culture rate, making early diagnosis and personalized treatment still a challenge for clinicians. Epidemiological studies on twins have shown that genetic factors are associated with neonatal sepsis. Gene polymorphisms are closely related to susceptibility, disease development, and prognosis. This article provides a review of gene polymorphisms related to neonatal sepsis, including interleukins, tumor necrosis factor, Toll-like receptors, NOD-like receptors, CD14, triggering receptor expressed on myeloid cells-1, mannose-binding lectin, and other immune proteins, aiming to promote precision medicine for this disease.
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Predisposición Genética a la Enfermedad , Sepsis Neonatal , Polimorfismo Genético , Humanos , Recién Nacido , Sepsis Neonatal/genética , Interleucinas/genéticaRESUMEN
Acute lymphoblastic leukemia (ALL), a leading cause of childhood cancer, targets immune system B and T cells. While understanding its causes is crucial, predicting susceptibility holds immense power for early diagnosis and intervention. This study explored the potential of interleukin 10 (IL-10), a key immune regulator, as a predictive tool in Egyptian children. Investigating 100 ALL patients and 100 healthy controls, we analyzed the IL10 gene polymorphism (-1082 A/G) and serum levels. Strikingly, both the G allele and higher serum IL-10 levels were significantly associated with increased ALL risk (p < 0.05, OR > 1). Moreover, IL-10 emerged as a remarkably accurate predictor, boasting an AUC of 0.995, with a sensitivity of 97% and specificity of 96%. These findings unveil the potential of IL-10 as a powerful predictive tool for pediatric ALL in the studied Egyptian population. Identifying individuals with the GG/AG haplotype and elevated IL-10 levels could enable early intervention and potentially improve outcomes. While further validation in larger and more diverse populations is needed, this study paves the way for personalized risk assessment and potentially revolutionizes how we combat this childhood killer.
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Predisposición Genética a la Enfermedad , Interleucina-10 , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Interleucina-10/genética , Interleucina-10/sangre , Masculino , Femenino , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Niño , Medición de Riesgo/métodos , Preescolar , Egipto/epidemiología , Polimorfismo de Nucleótido Simple , Estudios de Casos y Controles , Lactante , Alelos , Adolescente , Genotipo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/sangreRESUMEN
OBJECTIVE: This study aimed to explore the potential role of CYP3A5 (c. 6986A>G) gene polymorphism in predicting kidney function impairment in patients with hypertension who did not have elevated serum cystatin C. METHODS: We recruited a group of patients with hypertension who did not have elevated cystatin C and analyzed the CYP3A5 (c. 6986A>G) gene polymorphism. Chi-square tests were used to compare the clinical characteristics and genotypic distribution between the two groups. Logistic regression analysis was used to explore the association between CYP3A5 (c.6986A>G) gene polymorphism and renal function impairment in hypertension with non-elevated cystatin. RESULTS: In patients with hypertension who participated in the study, there was a significant association between CYP3A5 (c. 6986A>G) gene polymorphism and kidney function impairment (p < 0.05). Patients with the CYP3A5 (c. 6986A>G) mutation display a greater risk of kidney function impairment. CONCLUSION: CYP3A5 (c. 6986A>G) gene AA homozygote polymorphism significantly increases risk of kidney function impairment in patients with hypertension with normal cystatin C. However, further studies are needed to validate this association and to further understand the mechanism of CYP3A5 (c. 6986A>G) gene polymorphism in kidney function impairment in patients with hypertension.
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Biomarcadores , Cistatina C , Citocromo P-450 CYP3A , Predisposición Genética a la Enfermedad , Hipertensión , Riñón , Polimorfismo de Nucleótido Simple , Humanos , Citocromo P-450 CYP3A/genética , Masculino , Femenino , Persona de Mediana Edad , Hipertensión/genética , Hipertensión/fisiopatología , Hipertensión/diagnóstico , Cistatina C/sangre , Cistatina C/genética , Biomarcadores/sangre , Factores de Riesgo , Riñón/fisiopatología , Fenotipo , Estudios de Asociación Genética , Homocigoto , Adulto , Anciano , Enfermedades Renales/genética , Enfermedades Renales/diagnóstico , Enfermedades Renales/sangre , Enfermedades Renales/fisiopatología , Enfermedades Renales/enzimología , Frecuencia de los Genes , Estudios de Casos y Controles , Medición de RiesgoRESUMEN
PCOS is a heterogeneous, multifactorial endocrine disorder with a complex pathophysiology. It is a globally rising infertility disorder that affects a large percentage of women of reproductive age, with a relatively high prevalence of 8-13%. Genome-wide association studies have revealed associations of genetic variations with many diseases, including PCOS. The cellular activity of IL8 is mediated by the receptor CXCR2, and transcription of IL8 is controlled by TNF-α. Therefore, this study aimed to investigate the association of TNF-α, CCR5-delta32, and CXCR2 gene variations with PCOS. METHODOLOGY: In this case control study, we used amplification-refractory mutation system (ARMS)-PCR to detect and determine the presence of the polymorphic variants TNF-α, CCR5-delta32, and CXCR2 in the study subjects. These gene polymorphs may serve as critical candidate gene variants in PCOS pathogenesis and therapeutics. RESULTS: The case-control study's findings revealed that the majority of the biochemical and endocrine serum biomarkers examined in the investigation-including lipids (LDL, HDL, and cholesterol), T2DM markers (fasting glucose, free insulin, and HOMA-IR), and hormones (FSH, LH, testosterone, and progesterone)-exhibited statistically significant changes in PCOS patients. The distributions of TNF-α (rs1800629), CCR5-delta32, and CXCR2 (rs2230054) genotypes analyzed within PCOS patients and healthy controls in the considered population were significant (p < 0.05). The heterozygosity of CXCR2-CA, TNF-α GA, and CCR5(WT+Δ32*) genotypes was significantly associated with PCOS susceptibility, with high OR and p < 0.05 in the codominant model. Similarly, the A allele of the TNF-α and CXCR2 genes, along with the CCR5Δ32*(mutant) allele, was significantly associated with PCOS susceptibility, with high OR and p < 0.05. Likewise, the CXCR2 (CA+AA) vs CC genotype was associated with increased susceptibility to PCOS, with OR 2.25, p < 0.032. CONCLUSIONS: Our study concludes that TNF-α rs1800629G>A, CXCR2-rs2230054C>T, and CCR5-Delta32 rs333 are potential loci for developing PCOS in the Tabuk population. These findings might eventually be useful in identifying and classifying those who are at risk for PCOS. To validate these results, it is advised that further longitudinal studies be conducted in diverse ethnic populations and with larger sample sizes.
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BACKGROUND: The importance of long noncoding RNAs (lncRNAs) in various biological processes has been increasingly recognized in recent years. This study investigated how gene polymorphism in HOX transcript antisense RNA (HOTAIR) lncRNA affects the predisposition to chronic kidney disease (CKD). METHODS: This study comprised 150 patients with CKD and 150 healthy controls. A PCR-RFLP and ARMS-PCR techniques were used for genotyping the five target polymorphisms. RESULTS: According to our findings, rs4759314 confers strong protection against CKD in allelic, dominant, and codominant heterozygote genetic patterns. Furthermore, rs3816153 decreased CKD risk by 78% when TT versus GG, 55% when GG+GT versus TT, and 74% when GT versus TT+GG. In contrast, the CC+CT genotype [odds ratio (OR) = 1.66, 95% confidence intervals (CIs) = 1.05-2.63] and the T allele (OR = 1.50, 95% CI = 1.06-2.11) of rs12826786, as well as the TT genotype (OR = 2.52, 95% CI = 1.06-5.98) of rs3816153 markedly increased the risk of CKD in the Iranian population. Although no linkage disequilibrium was found between the studied variants, the Crs12826786Trs920778Grs1899663Grs4759314Grs3816153 haplotype was associated with a decreased risk of CKD by 86% (OR = 0.14, 95% CI = 0.03-0.66). CONCLUSION: The rs920778 was not correlated with CKD risk, whereas the HOTAIR rs4759314, rs12826786, rs1899663, and rs3816153 polymorphisms affected the risk of CKD in our population. It seems essential to conduct repeated studies across various ethnic groups to explore the link between HOTAIR variants and their impact on the disease outcome.
Asunto(s)
Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , ARN Largo no Codificante , Insuficiencia Renal Crónica , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios de Casos y Controles , Insuficiencia Renal Crónica/genética , ARN Largo no Codificante/genéticaRESUMEN
The E-proteinoid 3 receptor (PTGER3), a member of the prostaglandin E2 (PGE2) subtype receptor, belongs to the G-protein-coupled superfamily of receptors. Animal studies have demonstrated its involvement in salt sensitivity by regulating sodium reabsorption. This study aimed to investigate the association between genetic variants of PTGER3 and salt sensitivity, longitudinal blood pressure (BP) changes, and the incidence of hypertension in Chinese adults. A chronic salt intake intervention was conducted involving 514 adults from 124 families in the 2004 Baoji Salt-Sensitivity Study Cohort in northern China. These participants followed a 3-day regular baseline diet, followed by a 7-day low-salt diet (3.0 g/d) and a 7-day high-salt diet (18 g/d), and were subsequently followed for 14 years. The findings revealed a significant relationship between the single nucleotide polymorphism (SNP) rs17482751 of PTGER3 and diastolic blood pressure (DBP) response to high salt intervention. Additionally, SNPs rs11209733, rs3765894, and rs2268062 were significantly associated with longitudinal changes in systolic blood pressure (SBP), DBP, and mean arterial pressure (MAP) during the 14-year follow-up period. SNP rs6424414 was significantly associated with longitudinal changes in DBP over 14 years. Finally, SNP rs17482751 showed a significant correlation with the incidence of hypertension over 14 years. These results emphasize the significant role of PTGER3 gene polymorphism in salt sensitivity, longitudinal BP changes, and the development of hypertension in the Chinese population.
Asunto(s)
Presión Sanguínea , Hipertensión , Polimorfismo de Nucleótido Simple , Subtipo EP3 de Receptores de Prostaglandina E , Cloruro de Sodio Dietético , Humanos , Hipertensión/genética , Hipertensión/epidemiología , Hipertensión/fisiopatología , Masculino , Femenino , China/epidemiología , Incidencia , Adulto , Persona de Mediana Edad , Presión Sanguínea/genética , Presión Sanguínea/fisiología , Cloruro de Sodio Dietético/efectos adversos , Subtipo EP3 de Receptores de Prostaglandina E/genética , Estudios Longitudinales , Pueblo Asiatico/genética , Dieta Hiposódica/métodos , Pueblos del Este de AsiaRESUMEN
Introduction: IL-6 and IL-10 may affect the activity of cytochrome P450 (CYP) 3A enzymes involved in tacrolimus (Tac) metabolism. Moreover, the effect of IL-6 and IL-10 on Tac pharmacokinetics may differ with respect to the genetic variations in their genes.Aim: To examine the influence of IL-6 and IL-10 gene polymorphisms on Tac dose requirements and exposure over a 5-year period following kidney transplantation. Univariate and standard multivariate linear regression and Monte Carlo analysis were performed to investigate potential covariates influencing Tac dose-adjusted trough concentration (C0/D) in various post-transplantation periods.Materials & methods: IL-6 (-174G > C), IL-10 (-1082G > A, -819C > T and -592C > A) genotype, Tac daily dose, C0, C0/D and intrapatient variability data were collected from 113 patients.Results: Multivariate regression analysis and accompanied Monte Carlo simulation underscore the importance of considering IL-6 -174G > C and IL-10 -1082G > A gene polymorphisms, alongside Tac metabolic phenotype and post-transplantation period, when tailoring Tac dosage regimen.Conclusion: This study provides valuable insights regarding the individualized adjustment of Tac treatment in various post-transplantation periods.
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