Association of CAPN10 SNPs and Haplotypes with Polycystic Ovary Syndrome among South Indian Women

Dasgupta, Shilpi; Sirisha, P.; Neelaveni, K; Katragadda, Anuradha; Reddy, B. Mohan

doi:10.1371/journal.pone.0032192

Cited by 31 publications

(23 citation statements)

References 26 publications

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“…We focused on the candidate gene analysis of PCOS in the Indian context by analyzing a panel of six genes (Androgen receptor, Follistatin, Luteinizing hormone β subunit gene, Calpain10, Insulin receptor substrate‐1, and PPARγ ) involved in different pathological pathways ranging from steroid hormone effects, gonadotropin action and regulation, insulin action and secretion, as well as energy homeostasis. We initiated the analysis for testing the association pattern of each of the candidate genes individually with PCOS susceptibility (Dasgupta et al, ; Dasgupta et al, , b, c, d). While the Androgen receptor gene was analyzed for CAG repeat polymorphism (Dasgupta et al, ), all the other five genes were studied for the presence of SNPs and their respective association with PCOS (Dasgupta et al, , b, c, d).…”

Section: Introductionmentioning

confidence: 99%

“…We initiated the analysis for testing the association pattern of each of the candidate genes individually with PCOS susceptibility (Dasgupta et al, ; Dasgupta et al, , b, c, d). While the Androgen receptor gene was analyzed for CAG repeat polymorphism (Dasgupta et al, ), all the other five genes were studied for the presence of SNPs and their respective association with PCOS (Dasgupta et al, , b, c, d). In Follistatin gene, we could not identify any mutation or polymorphism in either the cases or controls (Dasgupta et al, ).…”

Section: Introductionmentioning

confidence: 99%

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The Role of Epistasis in the Etiology of Polycystic Ovary Syndrome among Indian Women: SNP‐SNP and SNP‐Environment Interactions

Dasgupta

Reddy

2013

Annals of Human Genetics

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SummaryPolycystic Ovary Syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. It is a heterogeneous androgen excess disorder determined by the interaction of multiple genetic and environmental factors. Our earlier analysis on a panel of six candidate genes (Androgen receptor CAG repeats, Follistatin, Luteinizing hormone β subunit, Calpain10, Insulin receptor substrate-1 and PPARγ ) based on 250 PCOS cases and 299 controls revealed significant association patterns with PCOS among South-Indian women. We report here for the first time, the SNP-SNP and SNP-environment interactions of these genes in the same cohort. Both multivariate logistic regression as well as epistasis analysis (using Multifactor dimensionality reduction software) yielded significant results (P < 0.05). All CAPN10 SNPs show association (either risk-conferring or protective) in the obese group, highlighting the importance of this gene in the PCOS pathophysiology. LHP7(LHβ) and UCSNP44(CAPN10) emerged to be the prominent SNPs in the SNP-SNP interaction analysis. The best SNP-SNP interaction model was obtained between CAPN10 UCSNP-44 and PPARγ His447His, implying a significant metabolic component in the PCOS pathology. Replicating our findings in BMI-specific cohorts in different ethnic populations would be warranted in future to identify the physiological networks in PCOS.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Role of Epistasis in the Etiology of Polycystic Ovary Syndrome among Indian Women: SNP‐SNP and SNP‐Environment Interactions

Dasgupta

Reddy

2013

Annals of Human Genetics

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“…Further this haplotype also showed association with increased insulin levels in African-American women with PCOS [64]. The UCSNP-44 has been found to be associated with increased PCOS risk in Indian [65], Turkish [66], and Spanish [67] populations as well as with indices of hyperandrogenemia and hyperinsulinemia [66,67] in afflicted women. Studies have also confirmed association of UCSNP-43 with PCOS as well as metabolic syndrome in PCOS [68,69].…”

Section: International Journal Of Medical Geneticsmentioning

confidence: 77%

Genetic Markers of Polycystic Ovary Syndrome: Emphasis on Insulin Resistance

Shaikh

Dadachanji

Mukherjee

2014

International Journal of Medical Genetics

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Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of childbearing age causing not only reproductive but also metabolic anomalies. PCOS women present with ovulatory dysfunction, abnormal hormones, hyperandrogenemia, obesity, and hyperinsulinemia. It is a heterogeneous disorder which results from interaction of multiple genes along with environmental factors. Insulin resistance is a central key element contributing to PCOS pathogenesis and is further aggravated by obesity. Insulin regulates metabolic homeostasis and contributes to ovarian steroidogenesis. Candidate gene analyses have dissected genes related to insulin secretion and action for their association with PCOS susceptibility. Although a large number of genomic variants have been shown to be associated with PCOS, no single candidate gene has emerged as a convincing biomarker thus far. This may be attributed to large amount of heterogeneity observed in this disorder. This review presents an overview of the polymorphisms in genes related to insulin signaling and their association with PCOS and its related traits.

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“…The risk of CRC also increases with the degree of inflammation and duration of inflammatory colorectal diseases (duration/risk = 10 years/1.6%, 20 years/8.3%, and 30 years/18.4%) (Tanaka, 2012). CAPN10 is also associated with the risk of polycystic ovary syndrome (Dasgupta et al, 2012), pancreatic cancer (Fong et al, 2010), laryngeal cancer (Moreno-Luna et al, 2011), and prostate cancer (Meyer et al, 2010). The negative results of CAPN10 SNP43 and SNP19 on CRC risk in this study may due to the weak effect of single-locus or the small sample size.…”

Section: Discussionmentioning

confidence: 99%

Calpain-10 SNP43 and SNP19 Polymorphisms and Colorectal Cancer: a Matched Case-control Study

Yuan²,

Luan³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Objective: Insulin resistance (IR) is an established risk factor for colorectal cancer (CRC). Given that CRC and IR physiologically overlap and the calpain-10 gene (CAPN10) is a candidate for IR, we explored the association between CAPN10 and CRC risk. Methods: Blood samples of 400 case-control pairs were genotyped, and the lifestyle and dietary habits of these pairs were recorded and collected. Unconditional logistic regression (LR) was used to assess the effects of CAPN10 SNP43 and SNP19, and environmental factors. Both generalized multifactor dimensionality reduction (GMDR) and the classification and regression tree (CART) were used to test gene-environment interactions for CRC risk. Results: The GA+AA genotype of SNP43 and the Del/Ins+Ins/Ins genotype of SNP19 were marginally related to CRC risk (GA+AA: OR = 1.35, 95% CI = 0.92-1.99; Del/Ins+Ins/ Ins: OR = 1.31, 95% CI = 0.84-2.04). Notably, a high-order interaction was consistently identified by GMDR and CART analyses. In GMDR, the four-factor interaction model of SNP43, SNP19, red meat consumption, and smoked meat consumption was the best model, with a maximum cross-validation consistency of 10/10 and testing balance accuracy of 0.61 (P < 0.01). In LR, subjects with high red and smoked meat consumption and two risk genotypes had a 6.17-fold CRC risk (95% CI = 2.44-15.6) relative to that of subjects with low red and smoked meat consumption and null risk genotypes. In CART, individuals with high smoked and red meat consumption, SNP19 Del/Ins+Ins/Ins, and SNP43 GA+AA had higher CRC risk (OR = 4.56, 95%CI = 1.94-10.75) than those with low smoked and red meat consumption. Conclusions: Though the single loci of CAPN10 SNP43 and SNP19 are not enough to significantly increase the CRC susceptibility, the combination of SNP43, SNP19, red meat consumption, and smoked meat consumption is associated with elevated risk.

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Association of CAPN10 SNPs and Haplotypes with Polycystic Ovary Syndrome among South Indian Women

Cited by 31 publications

References 26 publications

The Role of Epistasis in the Etiology of Polycystic Ovary Syndrome among Indian Women: SNP‐SNP and SNP‐Environment Interactions

The Role of Epistasis in the Etiology of Polycystic Ovary Syndrome among Indian Women: SNP‐SNP and SNP‐Environment Interactions

Genetic Markers of Polycystic Ovary Syndrome: Emphasis on Insulin Resistance

Calpain-10 SNP43 and SNP19 Polymorphisms and Colorectal Cancer: a Matched Case-control Study

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