A meta-analysis on the association between PPAR-γ Pro12Ala polymorphism and polycystic ovary syndrome

He, Junli; Wang, Li; Liu, Junhong; Liu, Feng; Li, Xuliang

doi:10.1007/s10815-012-9772-4

Cited by 9 publications

(11 citation statements)

References 45 publications

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“…t-test was used to test the siginificance of the beta coefficient. p<0.05 is considered significant Recent meta-analyses reported the association of Pro12Ala with PCOS only in European but not in Asian populations [15,35] and further no association with HOMA-IR in PCOS women [35]. However, our findings highlight a significant association of Pro12Ala polymorphism with reduced susceptibility to PCOS as well as its association with reduced 2 h glucose levels in these Indian women.…”

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

confidence: 41%

“…Recent meta-analyses on Pro12Ala polymorphism of PPARγ have indicated that there are ethnic differences in association of this polymorphism with PCOS. 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].…”

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: Association Of Pparγ Pro12ala C/g Polymorphism With Pcos Andcontrasting

confidence: 41%

Section: Introductionmentioning

confidence: 99%

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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“…However, the merged results of several case-control studies revealed that the carriers of the polymorphic Ala allele have a lower risk of developing PCOS (32, 35,36). The difference between the findings of case studies and meta-analyses indicate that a very large sample size may be required to uncover the effect of genes that do not have a major genetic impact on PCOS, but rather represent genetically modifying factors.…”

Section: Discussionmentioning

confidence: 99%

“…Similar results were observed when analyzing the effect of the PPARG Pro12Ala on HOMA-IR. Two additional meta-analyses (35,36) concluded that the PPARG Pro12Ala variant may result in lower insulin levels, but exerts no effect on HOMA-IR in PCOS patients. These conflicting results may be explained by the differences in the genetic background of the population investigated and by gene-gene and gene-environmental interactions (i.e., diet, exercise and age) (40).…”

Section: Alelle (%) Genotype (%) ------------------------------------mentioning

confidence: 99%

Association of PPARG Pro12Ala polymorphism with insulin sensitivity and body mass index in patients with polycystic ovary syndrome

et al. 2013

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Abstract. Insulin resistance is one of the key factors in the pathogenesis of polycystic ovary syndrome (PCOS). The peroxisome proliferator-activated receptor gamma (PPARG) plays a role in the regulation of insulin sensitivity. The aim of the present study was to establish a possible association of the PPARG Pro12Ala polymorphism with PCOS and its effect on family and personal history, as well as on the metabolic and endocrine parameters in PCOS patients. A total of 151 PCOS patients and 179 healthy women of reproductive age were enrolled. History, body mass index (BMI), waist-to-hip ratio and the presence of phenotypic hyperandrogenism were recorded. Hormonal, metabolic and biochemical profiles were assessed. A molecular analysis for the genetic polymorphism was performed. One third (29.8%) of the PCOS patients were found to be carriers of at least one variant of the Ala allele (X/Ala), while 70.2% carried two wild-type Pro alleles (Pro/Pro), with an equal distribution observed in the control group. The PCOS patients carrying the X/Ala alleles exhibited lower serum fasting insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR) and BMI compared to Pro/Pro carriers. This finding was significant only in the lean PCOS group. The polymorphic genotype exerted no effect on history, hormonal and clinical hyperandrogenism, lipid status or C-reactive protein, leptin, adiponectin, resistin and ghrelin serum levels in women with PCOS. In conclusion, although the PPARG Pro12Ala polymorphism is not a major determinant of PCOS in the Croatian population, it may exert a positive effect on insulin sensitivity and BMI. As these associations were recorded exclusively in the lean group of patients with PCOS, this polymorphism potentially contributes to a protective role against hyperinsulinemia and obesity.

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“…On the contrary, studies in German, Chinese, Caucasian, and Greek population showed no association of this polymorphism with PCOS [81,[85][86][87][88][89][90]. A meta-analysis indicated Ala alleles reduce the probability of having PCOS in European populations but not in Asians, which included only Chinese and Korean studies [91,92]. Another polymorphism in PPAR gene, His 447His (C1431T) in exon 6, is reported to be frequent in PCOS women.…”

Section: Pparmentioning

confidence: 97%

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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A meta-analysis on the association between PPAR-γ Pro12Ala polymorphism and polycystic ovary syndrome

Cited by 9 publications

References 45 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

Association of PPARG Pro12Ala polymorphism with insulin sensitivity and body mass index in patients with polycystic ovary syndrome

Genetic Markers of Polycystic Ovary Syndrome: Emphasis on Insulin Resistance

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