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Asthma is a chronic respiratory disease characterized by coughing, wheezing, shortness of breath, chest tightness, overproduction of mucus, and expiratory airflow limitation, which affects >300 million people worldwide. It is triggered by the dynamic interplay of genetic factors and environmental exposure. Th17 cells are an emerging subset of CD4+ T cells, which secrete IL-17A. This proinflammatory cytokine has recently been associated with asthma, autoimmune diseases, and inflammatory disorders. The present case-control study was focused on identifying the involvement of the IL-17A gene in asthma pathogenesis among 150 clinically diagnosed asthma patients and 150 healthy controls (HCs) of South Indian origin. To carry out the study, we aimed to screen the genetic variants of rs2275913G/A and rs8193036C/T and also estimated the serum cytokine levels of the IL-17A cytokine of recruited subjects. Further, we evaluated mRNA expression in selected subjects to correlate with the genetic variants. The results revealed that the mean IL-17A serum levels (161.6 ± 380.1 pg/ml vs. 86.75 ± 90.01 pg/ml) and IgE levels (257.7 ± 133.3 pg/ml vs. 311.2 ± 160.5 pg/ml) in asthma patients were significantly high as compared to healthy controls (p < 0.05). The ROC curves were constructed to compare the cytokine levels of asthma patients and HC, and the area under the curve (AUC) for IL-17A cytokine was 0.64, indicating that the test was satisfactory and significant (95 % CI: 0.575-0.709; p < 0.001). Genotyping of rs2275913G/A polymorphism indicated a 1.6-fold risk (95 % CI-1.02-2.56; p = 0.04) for asthma patients compared to healthy controls, whereas no significant association was observed for rs8193036C/T polymorphism with asthma susceptibility. Under genetic models, GA and AA models showed a protective effect against the disease for rs2275913G/A. In contrast, no statistically significant result was observed among the models of rs8193036C/T when adjusted with age and sex. The mRNA expression levels of the gene were statistically high in patients compared to the HCs, with a 1.8-fold change (p < 0.0001). We conclude that the results indicate IL-17A rs2275913G/A is likely to contribute to protection against the disease, while IL-17A rs8193036C/T shows no association with the disease. However, no correlation was identified in serum cytokine levels concerning genotypes. This comprehensive information in the present study might contribute to developing novel therapeutic strategies for treating inflammatory diseases like asthma. Further studies are warranted to understand the diverse functions of IL-17A concerning its longitudinal stability and its response to clinical interventions with large sample sizes in various ethnicities.

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Around 20-28% of FMR1gene CGG premutation (PM) carriers are at augmented risk towards an infertility related disorder, Fragile X-associated primary ovarian insufficiency (FXPOI). Except the effect of CGG repeats, reports are not available on the mechanism through which the cis-acting variations, namely, SNPs involved in POI susceptibility. Addressing the hypothesis that the FMR1 gene polymorphisms [CGG repeats, rs25731(T > A) and rs4949(A > G)] might increase their individual and combined impact in disease predisposition, we tested the genetic variants in 200 south Indian DNA samples consists of 100 patients and 100 healthy volunteers. We used gene scan method to score the CGG repeat length, and ARMS and RFLP methods to genotype the SNPs. Only 0.5% of each Gray zone and PM alleles were found among patient group, however, no disease association was noticed with repeat length. The rs25731 showed protection [OR:0.32; (0.13-0.76), p = 0.006] and rs4949 reported a 2.5-fold risk towards the disease predisposition [OR:2.46; (1.06-5.74), p = 0.031] but, both found insignificant after Bonferroni correction was done under different Genetic Models. Novel classification of genotype combinations, 'Normal&Variant Homozygote' [OR:2.89,(1.12-7.9), p < 0.05] and 'Allele2-T-G' haplotype block (6%vs.1%, p = 0.08) were noticed to be at marginal risk for POI. We demonstrated a susceptible role of the combined effect of variant allele-G and Allele-2 (repeat allele outside the normal range) for FXPOI. To support our findings of its first kind, further studies with large samples are warranted in understanding the role of FMR1 genetic variants in FXPOI etio-pathophysiology, the outcome might help in providing better reproductive treatment options for females, who are at risk for FXPOI.

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BACKGROUND: Periodontal disease (PD), a chronic inflammatory disorder mediated by progressive destruction of the oral cavity is one of the key factors for many systemic disorders including Coronary Artery Disease (CAD). The upregulation of CDKN2BAS, a long noncoding RNA gene expression in gingival epithelial cells and gingival fibroblasts of periodontitis shows a strong correlation between the severity of atherosclerosis and PD. Considering the crucial role of CDKN2BAS gene polymorphisms (rs496892 G > A and rs7865618 A > G) and its expression the present study sought to identify the possible association with the disease predisposition in South Indian population. METHODS: For the present case-control study a total of 200 subjects that include 100 PD-CAD patients and 100 controls were recruited with prior consent. Genomic DNA and RNA were extracted and utilized for genotyping via ARMS-PCR and PCR-RFLP, and expression using RT-PCR respectively. RESULTS: The results showed a significant association of both the polymorphisms with that of the disease predisposition. The wild type genotypes (GG: OR-0.37; p-0.001; & AA: OR-0.29; p-0.005) conferred protection against the disease, whereas, the heterozygotes (GA: OR-2.45; p-0.004 & AG: OR-3.41; p-0.0001) conferred risk towards the disease, suggesting the involvement of the variant allele in disease causation. These results were further confirmed by haplotype analysis among A-G block (two variant alleles at both loci) with 2.5 fold risk (OR = 2.49, 95% CI = 1.16-5.36, p = 0.02) and G-G block (single risk allele at rs7865618 locus) with 3-fold risk (OR-3.0; p-0.01) towards the disease, suggesting the dominant involvement of rs7865618 in the disease causation. Though the expression of the CDKN2BAS gene is more in patients than controls, the variant genotypes among patients were evaluated to be down-regulated than the other genotypes. CONCLUSION: The present study concludes that the two selected polymorphisms have significant involvement individually and in interaction with each other in the disease predisposition. The expression studies also suggest that the selected polymorphisms in the 9p21.3 locus affect the CDKN2BAS gene expression. However, the results obtained in the present study should be confirmed with large samples in other ethnic cohorts.

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BACKGROUND: Dysfunctional regulation at immune checkpoints may lead to escape of the tumor cells and gives a scope to set in the unresolved Breast cancer (BC). The major anti-tumor retort is cell-mediated response which involves T lymphocytes. CTLA-4 (Cytotoxic T lymphocyte associated protein-4) with immune suppressive function and tolerance is associated with various autoimmune diseases and cancers including BC. The present study deals with CTLA-4 gene selected polymorphisms (rs11571317 C/T and rs3087243G/A) to explore their relation with breast cancer susceptibility and progression in BC patients. METHODS: For the present case-control study, we recruited a total of 570 women which include breast cancer patients and healthy control women from south India. Blood samples were collected, genomic DNA was isolated and genotyped by using PCR-RFLP method, and the data were analysed through suitable statistics. RESULTS: We observed a significant association of rs11571317 with BC in our study group, where CC genotype showed a three-fold increased risk towards BC and CT genotype to be protective. In-silico analyses strengthened our observation revealing the abolition of SP1 binding site in the CTLA-4 promoter by the mutant allele T. The CTLA-4 rs3087243 polymorphism showed an association not with the susceptibility but towards the tumor progression, where GG genotype was coupled with reduced tumor growth (OR = 0.01) and GA (OR = 6.2), AA (OR = 3.4) with increased tumor growth. The T-G haplotype was found to confer protection against breast cancer risk while C-A (OR = 3.6) and T-A (OR = 15.8) haplotypes were associated with disease progression. In-silico analysis for rs3087243 revealed change in threshold values between reference and variant sequences. CONCLUSION: The study suggests varied roles of different polymorphisms of CTLA-4 in the aetiopathogenesis of BC. Understanding the mechanism may help in the CTLA-4 based immunotherapy for BC.

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Background and Objectives. Cytokines regulate immune response and inflammation and play a crucial role in depigmentation process of vitiligo. The present study aimed to estimate the serum levels of pro- and anti-inflammatory cytokines, IFN-γ and IL-10, and their ratios in nonsegmental vitiligo patients and healthy individuals from India. Methods. Blood samples were collected from 280 subjects and serum IFN-γ and IL-10 levels were measured using standard ELISA. Results. Nonsegmental vitiligo patients showed increased levels of IFN-γ (12.4 ± 3.2 versus 9.9 ± 4.4 pg/mL) and decreased levels of IL-10 (9.3 ± 1.7 versus 11.5 ± 5 pg/mL) compared to controls. Ratio of IFN-γ : IL-10 differed significantly from patients to controls (p < 0.05). IFN-γ concentrations and IFN-γ : IL-10 ratio varied significantly with respect to clinical variants, disease stability, and social habits (smoking and alcohol consumption) and showed a positive correlation with disease duration. Family history of vitiligo was significantly associated with IFN-γ : IL-10 ratio but not with their individual levels. Conclusion. The ratio of IFN-γ : IL-10 serum levels may be considered as one of the promising immunological markers in nonsegmental vitiligo. This is the first study considering multiple aspects in relation to ratio of cytokine levels. Similar studies with large samples are warranted to confirm our observations.

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Pre-eclampsia (PE) is a pregnancy specific syndrome characterized by hypertension and proteinuria. Defective placentation during early stages of pregnancy in combination with maternal and environmental factors could lead to systemic inflammation, endothelial dysfunction and the manifestation of the clinical symptoms. HLA-G is considered essential for feto-maternal immune tolerance and successful placentation in pregnancy. ACE promotes decidualization, trophoblast proliferation and plays an important role in blood pressure homeostasis. The HLA-G 14bp and ACE IN/DEL polymorphisms have been reported to be associated with the development of pre-eclampsia (PE). The present study aimed at investigating the role of HLA-G and ACE gene polymorphisms in the aetiopathogenesis of PE. A total of 412 (206 PE patients and 206 normal pregnant women) blood samples were collected from Govt. maternity hospital, Hyderabad, India. Genotyping was carried out for both the genes using PCR followed by PAGE for HLA-G and AGE for ACE gene polymorphisms. DD(ACE) genotype was observed to be elevated (52.9% vs. 31.1%) in the patient group and ID(ACE) (29.6% vs. 54.8%) in the control group (p<0.05). However, HLA-G polymorphism did not differ between patients and controls (p>0.05). Further, combined genotype analysis revealed ID(HLA-G) DD(ACE) to be predisposing genotypes and ID(HLA-G) ID(ACE) to be protective toward preeclampsia in south Indian Women. The ACE genotype (DD(ACE)) is associated with high levels of angiotensin and seems to predispose the individual to PE. However, women carrying the intermediate levels of ACE and HLA-G associated combined genotype (ID(HLA-G) ID(HLA-G)) appear to be protective against developing PE.

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BACKGROUND: The rs3761548 polymorphism (-3279 C>A) of FOXP3 gene is associated with several autoimmune disorders. OBJECTIVE: We sought to determine whether rs3761548 polymorphism is associated with nondermatomal vitiligo in Indian subjects. METHODS: Genomic DNA was isolated from blood samples of 303 patients and 305 control subjects and genotyping was done by allele-specific primers. Data analysis was carried out for the entire cohort and separately for male and female participants as FOXP3 is an X-linked marker. Statistics were performed using software. RESULTS: The genotype frequencies differed significantly from patients to control subjects (P = .002). Further analysis demonstrated female participants with CC genotype were protected (CC vs CA+AA; odds ratio 0.38, 95% confidence interval 0.238-0.615) and those with CA genotype were at higher risk to develop vitiligo (CA vs CC+AA; odds ratio 2.634, 95% confidence interval 1.604-4.325). However, no such statistical difference was observed in male participants. LIMITATIONS: Our study is, to our knowledge, the first report from India with respect to vitiligo and rs3761548; however, we lack adequate literature assistance. CONCLUSIONS: The rs3761548 of FOXP3 gene in our population may be associated with susceptibility to vitiligo because of altered expression. CC genotype appears to be protective and CA genotype seems to impart nearly 3-fold risk to develop vitiligo in women and girls.

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Vitiligo is a depigmenting skin disorder with profound heterogenity in its aetio-pathophysiology, and is associated with inter-individual variation in progression of disease. Angiotensin converting enzyme (ACE) is a regulator of renin angiotensin system (RAS) that plays an important role in the physiology of the vasculature, blood pressure, inflammation, adipocyte distribution of various diseases. The present study was carried out in 243 vitiligo patients (132 males and 111 females), aged between 3-62 years with a mean age at onset of 21.6  ±  13.6 yrs, and in 205 healthy controls of south Indian origin. The main objectives of the present study were to evaluate the ACE I/D (insertion/deletion) polymorphism in the patient and control groups. Further, I/D genotypes were compared among the patients with and without the family history of vitiligo as well as the progression of the disease, through polymerase chain reaction (PCR) methods.

The results revealed a highly significant association of DD genotype with disease susceptibility (p < 0.01) in patients with a family history of vitiligo (p < 0.05) in terms of early age at onset. Further, the pre-dominance of ID genotype among patients revealed its association with a slow progression of the disease (p < 0.05). The present study is the first report to highlight the protective role of II genotype and the significant association of ID genotype with slow progression of the disease.

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