RESUMO
Growth factors are polypeptides that are critical for the initiation, progression, and metastasis of cancer. Most tumor cells are capable of synthesizing particular growth factors leading to constitutive pathway activation in these cells through autocrine signaling. Epidermal growth factor (EGF) is a potent mitogenic peptide that exerts direct effects on the proliferation and differentiation of tumor cells in carcinogenesis. By contrast, vascular endothelial growth factor (VEGF) is vital for the invasion and metastasis of neoplasms through the formation of new blood vessels from mature endothelial cells. In this study, we investigated the association between functional polymorphisms of both the EGF and VEGF genes and colorectal cancer (CRC) susceptibility. A total of 130 CRC patients and 212 healthy controls were recruited for this case-control study. Genotyping of genetic variants was conducted via real-time polymerase chain reaction (PCR) amplification with allele-specific TaqMan probes. None of the genotypes of the EGF +61 A>G and VEGF +936 C>T variants was significantly associated with CRC susceptibility among the Malaysian subjects evaluated (P > 0.05). The observed frequency distributions of the EGF +61 A>G polymorphism genotypes showed ethnic heterogeneity, which was not the case for the VEGF +936 C>T genotypes. In conclusion, no positive correlation between these functional polymorphisms and CRC risk was found in this Malaysian population. Studies of the EGF and VEGF genes and CRC susceptibility are scarce, and the results reported thus far differ from one population to another. Hence, more replication studies are warranted before any firm conclusions can be made.
Assuntos
Neoplasias Colorretais/genética , Fator de Crescimento Epidérmico/genética , Predisposição Genética para Doença , Polimorfismo Genético , Fator A de Crescimento do Endotélio Vascular/genética , Alelos , Povo Asiático , Estudos de Casos e Controles , Neoplasias Colorretais/epidemiologia , Frequência do Gene , Genótipo , Humanos , Malásia/epidemiologia , Razão de ChancesRESUMO
Colorectal cancer (CRC) is one of the most common types of cancer in both developed and developing countries. This disease is triggered by and progresses via the sequential accumulation of multiple genetic alterations. In addition, the interaction between low-penetrance genes and environmental factors can also increase the risk of developing CRC. Since inflammatory bowel diseases (IBDs) are one of the predisposing factors for CRC, IBD-related genes might, to a certain extent, be associated with cancer initiation. The nucleotide oligomerization domain 2/caspase activating recruitment domain 15 gene (NOD2/CARD15) is the most well-established gene to be associated with increased susceptibility to Crohn's disease. Thus, various studies have been performed to investigate the potential contribution of this gene to CRC risk. In this study, we aimed to determine the frequency of the Arg702Trp, Gly908Arg, 3020insC, Pro268Ser, and JW1 variants of NOD2/CARD15, and to investigate their association with CRC susceptibility. A total of 130 CRC patients and 212 healthy controls were recruited for this study. Subsequently, real-time polymerase chain reaction with TaqMan was performed for the genotyping of these NOD2/ CARD15 variants. None of the NOD2/CARD15 variants was statistically associated to CRC susceptibility in our Malaysian population. Our findings were remarkably similar to those of other Asian cohorts, which indicated that these NOD2/CARD15 variants exhibit genetic heterogeneity between Caucasian and Asian populations.
Assuntos
Povo Asiático/genética , Neoplasias Colorretais/genética , Variação Genética , Proteína Adaptadora de Sinalização NOD2/genética , Alelos , Estudos de Casos e Controles , Frequência do Gene , Estudos de Associação Genética , Heterogeneidade Genética , Predisposição Genética para Doença , Genótipo , Humanos , Malásia , Razão de Chances , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Mutations in the PAX6 gene that cause aniridia have been identified in various ethnicities but not in the Malaysian population. Therefore, the objective of this study was to investigate the PAX6 mutation in a Malaysian family with congenital aniridia. In this study, a complete ophthalmic examination was performed on a Dusun ethnic family with aniridia. Genomic DNA was extracted from the peripheral blood of the subjects and screened for the PAX6 gene mutation using polymerase chain reaction amplification high-resolution melting curve analysis (PCR-HRM) followed by confirmation via direct DNA sequencing. A heterozygous G deletion (c.857delG) in exon 7 causing a frame shift in PAX6 was identified in all affected family members. Genotype-phenotype correlation analysis revealed congenital cataract and all affected family members showed a similar spectrum of aniridia with no phenotypic variability but with differences in severity that were age-dependent. In summary, by using a PCR-HRM approach, this study is the first to report a PAX6 mutation in a Malaysian family. This mutation is the cause of the aniridia spectra observed in this family and of congenital cataract.
Assuntos
Aniridia/genética , Proteínas do Olho/genética , Sequenciamento de Nucleotídeos em Larga Escala , Proteínas de Homeodomínio/genética , Fatores de Transcrição Box Pareados/genética , Polimorfismo Conformacional de Fita Simples/genética , Proteínas Repressoras/genética , Aniridia/patologia , Povo Asiático/genética , Feminino , Estudos de Associação Genética , Humanos , Malásia , Masculino , Mutação , Desnaturação de Ácido Nucleico , Fator de Transcrição PAX6 , LinhagemRESUMO
Beta-thalassemia is a life-threatening inherited blood disorder. Rapid characterization of ß-globin gene mutations is necessary because of the high frequency of Malaysian ß-thalassemia carriers. A combination real-time polymerase chain reaction genotyping assay using TaqMan probes was developed to confirm ß-globin gene mutations. In this study, primers and probes were designed to specifically identify 8 common ß-thalassemia mutations in the Malaysian Malay and Chinese ethnic groups using the Primer Express software. "Blind tests" using DNA samples from healthy individuals and ß-thalassemia patients with different genotypes were performed to determine the specificity and sensitivity of this newly designed assay. Our results showed 100% sensitivity and specificity for this novel assay. In conclusion, the TaqMan genotyping assay is a straightforward assay that allows detection of ß-globin gene mutations in less than 40 min. The simplicity and reproducibility of the TaqMan genotyping assay permit its use in laboratories as a rapid and cost-effective diagnostic tool for confirmation of common ß-thalassemia mutations in Malaysia.
Assuntos
Povo Asiático/genética , Técnicas de Genotipagem/métodos , Mutação , Talassemia beta/genética , Povo Asiático/etnologia , Estudos de Casos e Controles , Haptoglobinas/genética , Humanos , Malásia , Reação em Cadeia da Polimerase/métodos , Sensibilidade e Especificidade , Método Simples-Cego , Talassemia beta/etnologiaRESUMO
This study aimed to investigate the potential association of TYK2 and STAT3 genes with the susceptibility to Crohn's disease (CD) among Malaysians. DNA samples were obtained from 80 CD patients and 100 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism methods were employed for genotyping, followed by statistical analysis. In our current study, none of the single nucleotide polymorphisms of either TYK2 or STAT3 was statistically associated with the susceptibility to CD in our local population (P > 0.05). In contrast, there was a statistically significant association between the G/G homozygotes of the STAT3 rs2293152 and the healthy control group (χ(2) = 6.229, P < 0.05). In conclusion, our study does not support the role of the TYK2 and STAT3 genes influencing CD susceptibility.
Assuntos
Povo Asiático/genética , Doença de Crohn/genética , Fator de Transcrição STAT3/genética , TYK2 Quinase/genética , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Heterozigoto , Homozigoto , Humanos , Malásia , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Crohn's disease is a chronic, relapsing inflammatory bowel disease; it affects the mucosa and deeper layers of the digestive wall. Two Crohn's disease patients who carried the JW1 variant and two patients who carried the SNP5 variant were investigated for other co-inherited polymorphisms that could influence Crohn's disease development. Based on the sequencing results, a homozygous 5'-UTR-59 G to A variant in exon 1 (SNP6) was observed in a patient who carried SNP5, while a heterozygous SNP6 variant was detected in the other patient who carried SNP5. No other associated mutations or polymorphisms were detected in the two patients who carried the JW1 variant of the CARD15/NOD2 gene.
Assuntos
Doença de Crohn/genética , Variação Genética , Padrões de Herança/genética , Mutação/genética , Regiões 5' não Traduzidas/genética , Sequência de Bases , Análise Mutacional de DNA , Éxons/genética , Humanos , Integrina alfaV/genética , Malásia , Dados de Sequência MolecularRESUMO
Studies of genetic mutations that have been used in predicting glioma prognosis have revealed a complex relationship between clinical and genetic factors. Epidermal growth factor (EGF) and the NAT2 gene play a central role in carcinogenesis. An adenine (A) to guanine (G) single nucleotide polymorphism at position 61 in the 5'-untranslated region (5'-UTR) of the EGF gene has been found to be associated with levels of EGF production, and the mutations in the NAT2 gene have been postulated as a risk factor for cancer. We investigated EGF and the NAT2 gene in 13 glioma tissue samples and 12 normal controls. In the EGF 5'-UTR 61G polymorphism, the heterozygote GA was the most common genotype in the glioma patients. In the NAT2 polymorphism at nucleotide position 857G/A, the G allele and the GG genotype were the most prevalent forms in both the glioma and normal samples. We did not find any homozygous AA genotypes in the glioma patients. Based on this preliminary evidence, the EGF 5'-UTR at position 61 and the NAT2 SNP at position 857 polymorphisms are associated with increased risk for glioma.
Assuntos
Regiões 5' não Traduzidas/genética , Arilamina N-Acetiltransferase/genética , Neoplasias Encefálicas/genética , Fator de Crescimento Epidérmico/genética , Predisposição Genética para Doença , Glioma/genética , Polimorfismo de Nucleotídeo Único/genética , Alelos , Neoplasias Encefálicas/enzimologia , Estudos de Casos e Controles , Eletroforese em Gel de Ágar , Frequência do Gene/genética , Estudos de Associação Genética , Glioma/enzimologia , Humanos , Malásia , Nucleotídeos/genética , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de RestriçãoRESUMO
Systemic lupus erythematosus (SLE) is an autoimmune disease that causes systemic damage, involving auto-reactive antibodies and over-deposition of immune complexes. Susceptibility to SLE is believed to be multifactorial, and genetics is one of the proven etiological factors; it can affect SLE development, severity and prognosis. We investigated a possible association between the angiotensin-converting enzyme gene and susceptibility to SLE in the Malaysian population. PCR was employed for the determination of I/D dimorphism of this gene. The I allele was more frequent than the D allele in both the SLE patients (N = 170) and healthy controls (N = 190). However, there was no significant difference in the distribution of these two alleles between both groups studied (χ(2) = 0.284, P > 0.05). Interestingly, the DD homozygous genotype scored notably higher in the healthy control group (χ(2) = 7.568, P < 0.05), while the ID heterozygote was observed to be significantly associated with SLE (χ(2) = 11.143, P < 0.05). In conclusion, with respect to the Malaysian population, the DD genotype might play a protective role in the development of SLE while in contrast, those who carry the ID genotype might be at potential risk for onset of this disease.
Assuntos
Lúpus Eritematoso Sistêmico/genética , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Sequência de Bases , Estudos de Casos e Controles , Primers do DNA , Heterozigoto , Humanos , Malásia , Reação em Cadeia da PolimeraseRESUMO
Hemagglutinin (HA) protein plays an important role in binding the influenza virus to infected cells and therefore mediates infection. Deposited HA sequences of 86 Asian strains of influenza A (H1N1) viruses during the first outbreak were obtained from the NCBI database and compared. Interaction of the HA protein of influenza A (H1N1) virus with the human sialic acid receptor was also studied using bioinformatics. Overall, not more than three single-point amino acid variants/changes were observed in the HA protein region of influenza A (H1N1) virus from Asian countries when a selected group sequence comparison was made. The bioinformatics study showed that the HA protein of influenza A (H1N1) binds to the sialic acid receptor in human airway receptors, possibly key to air-borne infection in humans.
Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Vírus da Influenza A Subtipo H1N1/metabolismo , Ácido N-Acetilneuramínico/metabolismo , Receptores Virais/metabolismo , Substituição de Aminoácidos , Ásia , Sítios de Ligação , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Humanos , Ligação de Hidrogênio , Vírus da Influenza A Subtipo H1N1/genética , Modelos Moleculares , Mutação , Ácido N-Acetilneuramínico/química , Ligação ProteicaRESUMO
Diabetic retinopathy is the most common diabetic eye disease, occurring in about 60% of type 2 diabetic patients. Other than known clinical risk factors, the influence of genes has been suggested as part of the development of diabetic retinopathy. We investigated the association of Gly82Ser, 1704G/T and 2184A/G polymorphisms in the RAGE gene with retinopathy in type 2 diabetic patients in Malaysia. Ninety-eight unrelated retinopathy patients and 185 unrelated healthy controls from all over Malaysia were recruited in this study. The allele and genotype frequencies of the three gene polymorphisms were investigated using PCR-RFLP. The allele frequency of the three polymorphisms did not differ significantly between the control and the retinopathy group (P > 0.05). Analysis of the frequency of GA+AA, GT+TT and AG+GG in the retinopathy group did not reveal significant differences (P > 0.05) compared to the control group. We conclude that RAGE gene Gly82Ser, 1704G/T and 2184A/G polymorphisms are not associated with retinopathy development in the Malaysian population.
Assuntos
Diabetes Mellitus Tipo 2/genética , Retinopatia Diabética/genética , Polimorfismo de Nucleotídeo Único , Receptor para Produtos Finais de Glicação Avançada/genética , Adulto , Idoso , Alelos , Povo Asiático/genética , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Malásia , Masculino , Pessoa de Meia-IdadeRESUMO
Regulated on activation, normal T-cell expressed and secreted (RANTES) and stromal cell-derived factor 1 (SDF-1) are members of the CC- and CXC-chemokine families, respectively. Both genes have been postulated to be involved in the pathogenesis of systemic lupus erythematosus (SLE). We analyzed position 28 of the RANTES gene promoter region, as well as the SNP observed in the 3' UTR of the SDF-1 gene at position 801, in 130 patients presenting SLE at the Malaya University Medical Centre. Screening of 130 healthy volunteer controls using RFLP was also performed. RANTES-28 polymorphism analysis showed no significant (P = 0.3520) relationship, even though homozygous C/C was more frequent in SLE patients (OR = 1.4183) and heterozygous C/G was more frequent in healthy controls (OR = 0.7051). There were no significant (P = 0.2650) associations between A/A (OR = 0.783), G/G (OR = 1.5914) and G/A (OR = 0.8289) genotypes in the SDF-1 gene polymorphism with SLE. We conclude that there is no significant association of RANTES-28 and SDF-1 gene polymorphisms and occurrence of SLE in Malaysia.
Assuntos
Quimiocina CCL5/genética , Quimiocina CXCL12/genética , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Regiões 3' não Traduzidas/genética , Adolescente , Adulto , Povo Asiático/etnologia , Povo Asiático/genética , Feminino , Humanos , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/etnologia , Malásia/epidemiologia , Malásia/etnologia , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genéticaRESUMO
Allele frequencies of 15 short tandem repeat (STR) loci, namely D5S818, D7S820, D13S317, D16S539, TH01, TPOX, Penta D, Penta E, D3S1358, D8S1179, D18S51, D21S11, CSF1PO, vWA, and FGA, were determined for 154 individuals from the Kadazan-Dusun tribe, an indigenous population of East Malaysia. All loci were amplified by polymerase chain reaction, using the Powerplex 16 system. Alleles were typed using a gene analyzer and the Genemapper ID software. Various statistical parameters were calculated and the combined power of discrimination for the 15 loci in the population was calculated as 0.999999999999999. These loci are thus, informative and can be used effectively in forensic and genetic studies of this indigenous population.
Assuntos
Frequência do Gene/genética , Repetições de Microssatélites , Alelos , Loci Gênicos , Genética Populacional , Humanos , Malásia/etnologia , Reação em Cadeia da PolimeraseRESUMO
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that involves the inflammation of various organs upon deposition of immune complexes and is characterized by uncontrolled B cell hyperactivity. Despite intensive research on the etiology of the disease, the exact cause of the onset of SLE is unknown. The pathogenesis of the disease has been proposed to be associated with the imbalance of T helper type 1 (Th1) and Th2 cytokine activities. Elevated serum levels of interleukin-6 (IL-6), a Th2 cytokine with various functions in the regulation of human biological systems, are observed in SLE patients. In the present study, 100 Malaysian SLE patients and 100 controls were evaluated in order to determine the association of polymorphisms existing in the promoter region of the IL-6 gene with the onset of SLE. The homozygous G genotype was found to be significant in SLE patients (χ² = 33.754; P = 0.00000000625), whereas the heterozygous G/C genotype was significant in the controls (χ²= 25.087; P = 0.000000548). We suggest that the C allele might have a masking effect on the G allele when both alleles are present in heterozygous individuals. However, we did not observe any significant association of the homozygous C allele with the onset of SLE or with protection from the disease (χ² = 1.684; P = 0.194366).
Assuntos
Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , /genética , Lúpus Eritematoso Sistêmico/genética , Estudos de Casos e Controles , Frequência do Gene , Homozigoto , /sangue , Lúpus Eritematoso Sistêmico/sangue , Malásia , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas , Polimorfismo de Nucleotídeo Único/genética , Adulto JovemRESUMO
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that involves the inflammation of various organs upon deposition of immune complexes and is characterized by uncontrolled B cell hyperactivity. Despite intensive research on the etiology of the disease, the exact cause of the onset of SLE is unknown. The pathogenesis of the disease has been proposed to be associated with the imbalance of T helper type 1 (Th1) and Th2 cytokine activities. Elevated serum levels of interleukin-6 (IL-6), a Th2 cytokine with various functions in the regulation of human biological systems, are observed in SLE patients. In the present study, 100 Malaysian SLE patients and 100 controls were evaluated in order to determine the association of polymorphisms existing in the promoter region of the IL-6 gene with the onset of SLE. The homozygous G genotype was found to be significant in SLE patients (chi(2) = 33.754; P = 0.00000000625), whereas the heterozygous G/C genotype was significant in the controls (chi(2)= 25.087; P = 0.000000548). We suggest that the C allele might have a masking effect on the G allele when both alleles are present in heterozygous individuals. However, we did not observe any significant association of the homozygous C allele with the onset of SLE or with protection from the disease (chi(2) = 1.684; P = 0.194366).
Assuntos
Interleucina-6/genética , Lúpus Eritematoso Sistêmico/genética , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Homozigoto , Humanos , Interleucina-6/sangue , Lúpus Eritematoso Sistêmico/sangue , Malásia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas , Adulto JovemRESUMO
Es artículo fue presentado en la publicación Aqua (No. 1/1997), da a conocer algunos resultados de un estudio en laboratorio de la formación de Trihalometanos en el agua potable (resultante de la reacción entre el cloro y la materia orgánico, generalmente de origen natural). Se describe el tratamiento actual y las posibilidades de la modelación de las distintas reacciones
Assuntos
Água , Purificação da Água , TrialometanosRESUMO
Es artículo fue presentado en la publicación Aqua (No. 1/1997), da a conocer algunos resultados de un estudio en laboratorio de la formación de Trihalometanos en el agua potable (resultante de la reacción entre el cloro y la materia orgánico, generalmente de origen natural). Se describe el tratamiento actual y las posibilidades de la modelación de las distintas reacciones