Shilpi Dasgupta

Publications (10) View all

• Article: The Role of Epistasis in the Etiology of Polycystic Ovary Syndrome among Indian Women: SNP-SNP and SNP-Environment Interactions.

  Shilpi Dasgupta, B Mohan Reddy
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  ABSTRACT: Polycystic 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.
  Annals of Human Genetics 04/2013; · 2.57 Impact Factor
• Article: Does follistatin gene have any direct role in the manifestation of polycystic ovary syndrome in Indian women?

  Shilpi Dasgupta, PVS Sirisha, K.Neelaveni, K.Anuradha, G.Sudhakar, B.M.Reddy
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  ABSTRACT: Background: Out of a panel of 37 candidate genes tested for linkage with polycystic ovary syndrome (PCOS), the strongest evidence of linkage was reported in the follistatin (FST) gene region. Subsequently, a couple of studies outside India investigated the FST gene for the presence of any mutations and its association with PCOS and the results were found to be largely inconsistent probably due to differences in the ethnic backgrounds and small sample sizes. Aims: To screen the FST gene for mutations and to establish their association pattern with PCOS among a large cohort of South Indian women. Settings and Design: Case-control study. Materials and Methods: PCOS cases were recruited according to the 2003 Rotterdam diagnostic criteria. All the exons of the FST gene were amplified and analyzed in all the cases and controls for the presence of mutations using polymerase chain reaction (PCR) and direct DNA sequencing. Results: A total of 549 women consisting of 250 PCOS cases and 299 controls were recruited for the study. No mutations were found in any of the exons of the FST gene in our Indian sample which is consistent with an earlier finding among the Asian women from Singapore. Although three of the four cohorts of Caucasian background studied earlier reported variants, none of them could establish a strong association with PCOS. Conclusions: The occurrence of the exonic variants of FST gene seems to be dependent on the ethnic background of the subjects under study and its role in the PCOS pathophysiology cannot be established with hitherto available evidence.
  Journal of Postgraduate Medicine 09/2012; 58(3):190-193. · 1.26 Impact Factor
• Article: Genetic factors influencing recurrent pregnancy loss: lessons learnt from recent studies

  Shilpi Dasgupta, Aruna Meka, Battini Mohan Reddy
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  ABSTRACT: Recurrent miscarriage (RM) is the loss of three or more consecutive pregnancies before the 24th week of gestation. RM occurs chiefly owing to either a problem with the pregnancy or the environment where it implants and further development occurs. A large number of pathological factors have been attributed to the etiology of RM. A number of genetic association studies in different populations, including that of India, have been conducted, yet with no definite conclusions. This review analyzes various genetic association studies that have been conducted based on the underlying immunological, thrombophilic and endocrine factors in RM, and outlines the salient features of the findings and lessons from those, suggesting possible future directions for research in this area.
  Expert Review of Obstetrics &amp Gynecology 07/2012; 7(4):363-378.
• Article: Polymorphisms in the IRS-1 and PPAR-γ genes and their association with polycystic ovary syndrome among South Indian women.

  Shilpi Dasgupta, Pisapati Sirisha, Kudugunti Neelaveni, Katragadda Anuradha, Godi Sudhakar, B Mohan Reddy
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  ABSTRACT: Polycystic ovary syndrome is known to be characterized by metabolic abnormalities such as hyperinsulinemia, adiposity and dyslipidemia. Both insulin receptor substrate-1 and peroxisome proliferator-activated receptor-γ have emerged as significant candidate genes in the pathogenesis of PCOS. In this study, we report for the first time, the association pattern of these genes with PCOS among South Indian women. Two hundred fifty PCOS cases and 299 controls were sequenced for IRS-1 exon1 and PPAR-γ exon 2 and exon 6 to study the already reported SNPs in other ethnic groups and to identify any novel SNP in these exonic regions specific to the Indian population. We did not find any novel SNP in our population except for those already reported- two IRS-1 polymorphisms (Gly972Arg and G2323A) and two PPAR-γ polymorphisms (Pro12Ala and His447His). While the IRS-1 polymorphic alleles had a similar distribution between cases and controls, the PPAR-γ exon 2 Ala allele and exon 6 His447His T allele were significantly more in the controls than in the cases (p≤0.05). Haplotype association analysis also suggests that both IRS-1 and PPAR-γ haplotypes with mutations depicted reduced frequency of hyperandrogenic and metabolic traits in PCOS compared to the haplotype with only wild type alleles. Our study on Indian women suggests that while IRS-1, contrary to the earlier findings in other ethnic groups, seems to have a probable protective role against development of specific PCOS sub-phenotypes, the evidence for a probable protective role of PPAR-γ is reaffirmed in our study.
  Gene 05/2012; 503(1):140-6. · 2.34 Impact Factor
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  Article: Association of CAPN10 SNPs and haplotypes with polycystic ovary syndrome among South Indian Women.

  Shilpi Dasgupta, Pisapati V S Sirisha, Kudugunti Neelaveni, Katragadda Anuradha, B Mohan Reddy
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  ABSTRACT: Polycystic Ovary Syndrome (PCOS) is known to be characterized by metabolic disorder in which hyperinsulinemia and peripheral insulin resistance are central features. Given the physiological overlap between PCOS and type-2 diabetes (T2DM), and calpain 10 gene (CAPN10) being a strong candidate for T2DM, a number of studies have analyzed CAPN10 SNPs among PCOS women yielding contradictory results. Our study is first of its kind to investigate the association pattern of CAPN10 polymorphisms (UCSNP-44, 43, 56, 19 and 63) with PCOS among Indian women. 250 PCOS cases and 299 controls from Southern India were recruited for this study. Allele and genotype frequencies of the SNPs were determined and compared between the cases and controls. Results show significant association of UCSNP-44 genotype CC with PCOS (p = 0.007) with highly significant odds ratio when compared to TC (OR = 2.51, p = 0.003, 95% CI = 1.37-4.61) as well as TT (OR = 1.94, p = 0.016, 95% CI = 1.13-3.34). While the haplotype carrying the SNP-44 and SNP-19 variants (21121) exhibited a 2 fold increase in the risk for PCOS (OR = 2.37, p = 0.03), the haplotype containing SNP-56 and SNP-19 variants (11221) seems to have a protective role against PCOS (OR = 0.20, p = 0.004). Our results support the earlier evidence for a possible role of UCSNP-44 of the CAPN10 gene in the manifestation of PCOS.
  PLoS ONE 01/2012; 7(2):e32192. · 4.09 Impact Factor