Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ gene in women with polycystic ovary syndrome

Yılmaz, Murat; Ergün, Meltem; Karakoç, Ayhan; Yurtçu, Erkan; Çakır, Nuri; Arslan, Metin

doi:10.1080/09513590600733357

Cited by 40 publications

(46 citation statements)

References 38 publications

(86 reference statements)

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“…A significantly lower occurrence of variant genotypes and lower Ala allele frequency of Pro12Ala polymorphism among PCOS women in our study cohort and its significant association with reduced risk of PCOS is in agreement with previous findings in Finnish [17], Turkish [34] and Korean [12] women. 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].…”

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

confidence: 81%

“…It is well established that Ala allele, enhances insulin sensitivity and protects against development of T2DM [28]. Increased insulin sensitivity, decreased fasting insulin levels, HOMA-IR, [13,14,17,30,34] basal metabolic rate [16] and increased HDL-C levels [4] were observed in women with PCOS who were carriers of Ala alleles. Consistently we too observed that the variant genotype carriers had significantly lower 2 h glucose levels than wild genotype carriers in PCOS group but not in controls.…”

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

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 Andsupporting

confidence: 81%

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

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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“…Problematic to genetic association studies are differences in ethnic background and small sample sizes, both of which can lead to spurious results. Whereas most studies (9)(10)(11)(12)14,15), present study included, reported no association between Pro12Ala genotype and PCOS diagnosis, a few reported that the Pro12Ala G allele was significantly less frequent in PCOS versus control women (13,16). Additionally, some studies reported significant increases in insulin sensitivity (decreased HOMA-IR) and decreases in fasting insulin and glucose levels (8-10) and lower hirsutism score (9) in PCOS women with the Pro12Ala G allele; whereas others (7,11,14), including this study, reported no association with fasting glucose and insulin or changes in HOMA-IR in those with PCOS.…”

Section: Discussionmentioning

confidence: 64%

Genetic variants in peroxisome proliferator-activated receptor gamma influence insulin resistance and testosterone levels in normal women, but not those with polycystic ovary syndrome

Antoine

Pall

Trader

et al. 2007

Fertility and Sterility

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Polymorphisms in PPARG implicated in previous studies of metabolic traits do not appear to influence component phenotypes of PCOS, but do affect androgens and insulin resistance in the general population.Objective-To investigate the relationship of the PPARG Pro12Ala and silent exon 6 (His447His) polymorphisms with the clinical features of polycystic ovary syndrome (PCOS).Design-PCOS and control subjects were genotyped for Pro12Ala and His447His; associations between genotype, diagnosis, and hormonal/metabolic parameters were assessed.Setting-Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; control subjects were recruited from the surrounding community. Genotyping was performed at Cedars-Sinai Medical Center in Los Angeles.Reprint Request: Mark O. Goodarzi, M.D., Ph.D., Cedars-Sinai Medical Center, Division of Endocrinology, Diabetes and Metabolism, 8700 Beverly Blvd., Los Angeles, CA 90048, email: mark.goodarzi@cshs.org Presented in part at the 87 th Annual Meeting of the Endocrine Society, San Diego, June 4-7, 2005 Supported by:This study was supported in part by the Helping Hand of Los Angeles, and by grants R01-HD29364 and K24-HD01346 from the National Institutes of Health (to RA). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Result(s)-Pro12Ala and His447His did not influence risk of PCOS or its component phenotypes in PCOS patients. In controls, Pro12Ala did not influence measures of insulin resistance or androgen production; however, carriers of the His447His T allele had significantly decreased free and total testosterone levels and HOMA-IR. Furthermore, haplotypes in controls bearing the His447His T allele were also associated with decreased testosterone. Conflict of Interest NIH Public AccessConclusion(s)-does not appear to be an important modifier gene in PCOS. In controls, however, the His447His T allele may be in linkage disequilibrium with a functional variant that influences insulin resistance and testosterone production. Keywordsperoxisome proliferator activated receptor gamma; polycystic ovary syndrome; single nucleotide polymorphism; testosterone; insulin resistance Polycystic ovary syndrome (PCOS) is a common disorder affecting 6-8% of reproductive aged women (1) and clinically manifests as menstrual irregularities, hyperandrogenism, polycystic ovaries, and often obesity. Several studies demonstrate substantial familial aggregation of PCOS with most showing significantly higher rates of PCOS among first-degree relatives when compared to the general population (2,3). Fifty to s...

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“…Distribution of PPARG Pro12Ala alleles and genotypes in PCOS patients and controls. the European population (25)(26)(27)(28)(29)(31)(32)(33)(34). To the best of our knowledge, the highest prevalence of the PPARG Pro12Ala polymorphism was reported in the Polish (23,15%) (37) and the Slovenian populations (27,5%) (38).…”

Section: Discussionmentioning

confidence: 99%

“…Although certain studies demonstrated a lower frequency of PPARG Pro12Ala polymorphism among PCOS patients (24)(25)(26), the majority of case-control studies (27)(28)(29)(30)(31)(32)(33)(34) reported no significant differences. 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).…”

Section: Discussionmentioning

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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Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ gene in women with polycystic ovary syndrome

Abstract: We suggest that Pro12Ala polymorphism of the PPAR-gamma gene may be a modifier of insulin resistance in women with PCOS.

Cited by 40 publications

References 38 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

Genetic variants in peroxisome proliferator-activated receptor gamma influence insulin resistance and testosterone levels in normal women, but not those with polycystic ovary syndrome

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

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