Polymorphisms in the IRS‐1 and PPAR-γ genes and their association with polycystic ovary syndrome among South Indian women

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

doi:10.1016/j.gene.2012.04.060

Cited by 26 publications

(32 citation statements)

References 42 publications

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“…Conversely, decreased levels of testosterone, insulin and IR were associated with this polymorphism in healthy controls but not women with PCOS in Caucasian population [1]. Allelic (p=0.03) but not genotypic (p=0.18) association of His447His polymorphism was reported with PCOS risk in South Indian women [6] however, we observed significant difference in both allelic and genotypic frequency between PCOS and controls, though not corroborated by logistic regression analysis. Genotype-phenotype association showed that variant genotype carriers of this polymorphism had better insulin related traits such as lower fasting insulin, HOMA-IR and 2 h glucose levels relative to wild genotype carriers only among PCOS subjects but not in controls.…”

Section: Relationship Of Pparγ His447hisc/t Polymorphism With Pcos Ancontrasting

confidence: 74%

“…Recently, a study from South India showed marginally significant difference in allelic (p=0.05) but not in the genotypic frequency (p=0.23) of this polymorphism in PCOS women (n=243) as compared to controls (n=281) [6]. However, in our study with increased sample size of PCOS women (n=450) and controls (n=300), a significant difference in both allelic and genotypic frequency were found; and further logistic regression analysis also revealed a stronger association of Pro12Ala polymorphism with reduced susceptibility to PCOS.…”

Section: Association Of Pparγ Pro12ala C/g Polymorphism With Pcos Andmentioning

confidence: 95%

“…The second polymorphism, His447His of PPARγ is a synonymous SNP, reported to be associated with PCOS risk in Italian [21], Korean [12] and South Indian women [6] but not in Caucasian [1] and Greek [5] women. The association of this polymorphism with PCOS phenotypes too has been ambiguous.…”

Section: Relationship Of Pparγ His447hisc/t Polymorphism With Pcos Anmentioning

confidence: 98%

“…The protective role of Pro12Ala against development of PCOS has been confirmed in European but not the Asian population [15,35] which include studies from China [32] and Korea [4]. A recent study in South Indian women showed probable protective effects of Pro12Ala on PCOS, emphasizing the investigative potential of this polymorphism in Indian women [6]. No other report exploring association of PPARγ polymorphisms in Indian women with PCOS and its related traits is available.…”

Section: Introductionmentioning

confidence: 99%

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Peroxisome proliferator activated receptor gamma gene variants influence susceptibility and insulin related traits in Indian women with polycystic ovary syndrome

Shaikh

Mukherjee

Shah³

et al. 2013

J Assist Reprod Genet

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Purpose Peroxisome proliferator activated receptor gamma (PPARγ), a transcription factor involved in glucose and lipid metabolism is one of the candidate genes associated with polycystic ovary syndrome (PCOS). We investigated individual and combined associations of Pro12Ala and His447His polymorphisms of PPARγ with PCOS susceptibility and its related traits (hyperinsulinemia, hyperandrogenemia and lipid parameters) in Indian women.Method Genotyping of PPARγ polymorphisms in this casecontrol study was performed in PCOS (n=450) and agematched controls (n=300) by direct sequencing. Clinical, anthropometric, hormonal and metabolic parameters were estimated in 275 women with PCOS and 169 controls. Chisquare test was used to compare the categorical data while regression analysis was used to evaluate association of genotypes with PCOS as well as its related phenotypes. Results The frequencies of CC and CG+GG genotypes of Pro12Ala (χ 2 =15.3, p<0.0001) and CC and CT+TT genotypes of His447His (χ 2 =12.7, p=0.0004) polymorphisms were significantly different between PCOS and controls. Logistic regression analysis revealed a significant association of PCOS with Pro12Ala but not the His447His polymorphism. Carriers of variant genotypes at both PPARγ loci showed significantly reduced 2 h glucose levels while carriers of variant His447His genotype showed lower fasting insulin and HOMA-IR levels in PCOS women. Conclusions Pro12Ala polymorphism of PPARγ showed significant association with decreased PCOS susceptibility. Both polymorphisms influenced insulin related traits (2 h glucose, fasting insulin and HOMA-IR) and improved glucose metabolism in these women. This is the first report to establish that variations in PPARγ gene influence the insulin resistance pathophysiology in Indian women with PCOS.

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Section: Relationship Of Pparγ His447hisc/t Polymorphism With Pcos Ancontrasting

confidence: 74%

Section: Association Of Pparγ Pro12ala C/g Polymorphism With Pcos Andmentioning

confidence: 95%

Section: Relationship Of Pparγ His447hisc/t Polymorphism With Pcos Anmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Peroxisome proliferator activated receptor gamma gene variants influence susceptibility and insulin related traits in Indian women with polycystic ovary syndrome

Shaikh

Mukherjee

Shah³

et al. 2013

J Assist Reprod Genet

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“…The absence of significant association between hyperandrogenemia and insulin resistance in some recent studies have further supported this view [21]. Multiple studies throughout the world indicated that several factors including ethnicity might contribute to these different inferences due to genetic polymorphisms [22][23][24] stressing on the fact that the association between metabolic and neuroendocrinological abnormalities with PCOS may vary between different population groups in different areas. However, only a few studies are available from the South Asian countries and the Indian subcontinent that provided information regarding the differential relationship between the neuroendocrinological and metabolic profile among PCOS patients in these regions [25,26].…”

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confidence: 93%

Predictors of Insulin Resistance and Metabolic Complications in Polycystic Ovarian Syndrome in an Eastern Indian Population

et al. 2012

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The purpose of this study was to assess the predictive values of central obesity and hyperandrogenemia in development of insulin resistance and dyslipidemia in the polycystic ovarian syndrome (PCOS) patients in our region. Differences of fasting blood glucose level, insulin resistance index HOMA-IR, lipid parameters, waist hip ratio (WHR), body mass index, LH/FSH ratio and testosterone levels between 45 PCOS cases and 35 age matched controls were obtained. Strength of association between different parameters in the case group was assayed by Pearson's correlation analysis. Dependence of insulin resistance and WHR on different predictors was assessed by multiple linear regression assay. Total cholesterol, LDL cholesterol, LH, FSH, LH/FSH ratio, WHR and insulin resistance were significantly higher in the case group (p \ 0.05). Serum testosterone showed strong correlation with insulin resistance and LH/FSH ratio (r = 0.432 and 0.747, p = 0.01 and 0.001 respectively) in the PCOS patients while WHR and serum testosterone level stood out to be most significant predictors for the insulin resistance (b = 0.361 and 0.498; p = 0.048 and 0.049 respectively). Hyperandrogenemia and central obesity were the major factors predicting development of insulin resistance and its related metabolic and cardiovascular complications in our PCOS patients. We suggest early monitoring for androgen level and WHR in these patients for predicting an ensuing insulin resistance and modulating the treatment procedure accordingly to minimise future cardiovascular risks.

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Pathophysiological roles of chronic low‐grade inflammation mediators in polycystic ovary syndrome

Rostamtabar

Esmaeilzadeh

Tourani

et al. 2020

Journal Cellular Physiology

161

109

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Polycystic ovary syndrome (PCOS) is the most common hormonal imbalance disease in reproductive-aged women. Its basic characteristics are ovulatory dysfunction and ovarian overproduction of androgens that lead to severe symptoms such as insulin resistance, hirsutism, infertility, and acne. Notwithstanding the disease burden, its underlying mechanisms remain unknown, and no causal therapeutic exists. In recent years, further studies showed that inflammation processes are involved in ovulation and play a key role in ovarian follicular dynamics. Visceral adipose tissue can cause

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Polymorphisms in the IRS‐1 and PPAR-γ genes and their association with polycystic ovary syndrome among South Indian women

Cited by 26 publications

References 42 publications

Peroxisome proliferator activated receptor gamma gene variants influence susceptibility and insulin related traits in Indian women with polycystic ovary syndrome

Peroxisome proliferator activated receptor gamma gene variants influence susceptibility and insulin related traits in Indian women with polycystic ovary syndrome

Predictors of Insulin Resistance and Metabolic Complications in Polycystic Ovarian Syndrome in an Eastern Indian Population

Pathophysiological roles of chronic low‐grade inflammation mediators in polycystic ovary syndrome

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