scholarly journals Association of +45G15G(T/G) and +276(G/T) polymorphisms in the ADIPOQ gene with polycystic ovary syndrome among Han Chinese women

2008 ◽  
Vol 158 (2) ◽  
pp. 255-260 ◽  
Author(s):  
Ning Zhang ◽  
Yu-Hua Shi ◽  
Cui-Fang Hao ◽  
Harvest F Gu ◽  
Yuan Li ◽  
...  

ObjectivePolycystic ovary syndrome (PCOS) is frequently associated with insulin resistance (IR) and consequently with increased risk of metabolic disorders. Adiponectin is the most abundant adipocytokine and may play a role in the regulation of insulin sensitivity and IR in PCOS. The aim of the present study was to evaluate the genetic influence of the adiponectin (ADIPOQ) gene polymorphisms in the development of PCOS among Han Chinese women.MethodsTwo single nucleotide polymorphisms (SNPs),+45G15G(T/G) and +276(G/T), in the ADIPOQ gene were genotyped in 120 patients with PCOS and 120 healthy control subjects. All of them were Han Chinese women.ResultsBoth SNPs were found to be significantly associated with PCOS (P=0.021, odds ratios=1.629, 95% confidence intervals: 1.074–2.469 and P=0.015, 1.576, 1.091–2.279 respectively). In SNP +276(G/T), the allele G was found to be significantly associated with increased fasting insulin levels, homeostasis model assessment to assess IR index, and area under the curve glucose levels, but decreased glucose and insulin ratio in the PCOS patients. Furthermore, the patients carrying genotypes G/G and G/T had significantly decreased levels of serum adiponectin (6.16±3.18 plus 5.93±3.23 vs 8.96±3.21 μg/ml, P=0.030) compared with the patients with genotype T/T.ConclusionsThe present study provides evidence that SNPs +45G15G(T/G) and +276(G/T) in the ADIPOQ gene are associated with PCOS in Han Chinese women. SNP +276(G/T) may contribute to an impact of insulin levels and IR, which are implicated in the susceptibility for PCOS.

2015 ◽  
Vol 172 (3) ◽  
pp. 227-233 ◽  
Author(s):  
Rong Ju ◽  
Wei Wu ◽  
Juan Fei ◽  
Yufeng Qin ◽  
Qiuqin Tang ◽  
...  

ObjectiveTo assess whether single nucleotide polymorphisms of HSD17B5 (AKR1C3) (rs1937845 and rs12529) and HSD17B6 (rs898611) are associated with polycystic ovary syndrome (PCOS) in a Chinese population.DesignA case–control study was conducted to investigate the relation between HSD17B5 and HSD17B6 polymorphisms and PCOS.MethodsIn this study, 335 patients with PCOS and 354 controls were recruited. The genotypes of HSD17B5 (rs1937845 and rs12529) and HSD17B6 (rs898611) were detected by the TaqMan method.Results and conclusionsWe found that the genotypic frequencies of the rs1937845 polymorphism were different in subjects with PCOS compared with control, with the CT genotype being more commonly found in patients with PCOS than in controls (P=0.005). We observed a significantly 1.74-fold higher risk of CT genotype in the polymorphism rs1937845 in women with PCOS vs the control group (adjusted odds ratio (OR), 1.74; 95% CI=1.19–2.54; P=0.005). A similar, significant 1.47-fold higher risk (adjusted OR, 1.47; 95% CI=1.07–2.03; P=0.018) was demonstrated for T allele of polymorphism rs1937845 associated with PCOS. In patients with PCOS, the rs12529 (G>C) and rs1937845 (C>T) polymorphisms were strongly associated with the high level of testosterone. The TT carriers of polymorphism rs1937845 had a significantly increased homeostatic model assessment-B% (HOMA-B%) (P=0.045) and that might be associated with the high risk of insulin resistance. However, no significant difference was found in genotype or allele distributions of the polymorphisms rs12529 of HSD17B5 and rs898611 of HSD17B6 between patients with PCOS and controls. Additionally, the two polymorphisms of HSD17B5 are associated with hyperandrogenemia in patients with PCOS. In conclusion, our findings showed a significant statistical association between HSD17B5 rs1937845 and PCOS risk in Chinese women. The CT genotype and T allele frequency are influenced significantly to a higher extent in patients with PCOS than controls. Further studies are needed to confirm the results and find out the exact molecular mechanism of the polymorphism on the risk of hyperandrogenemia and PCOS.


2010 ◽  
Vol 163 (3) ◽  
pp. 399-406 ◽  
Author(s):  
Tao Tao ◽  
Edmond P Wickham ◽  
WuQiang Fan ◽  
Jiejin Yang ◽  
Wei Liu

ObjectiveAdiponectin, an abundant adipokine with insulin-sensitizing properties, exists in different multimeric forms, including low-molecular weight, medium-molecular weight, and high-molecular weight (HMW) species. Alterations in the distribution of adiponectin multimers and the relationship between adiponectin multimers and insulin resistance (IR) in women with polycystic ovary syndrome (PCOS) remain unclear. The objective of this study was to compare adiponectin multimerization status and estimate insulin sensitivity in Chinese women with PCOS compared with age- and body mass index (BMI)-matched controls.MethodsCross-sectional study involving 64 Chinese women with PCOS and 59 normal women. Circulating total adiponectin and its multimeric forms were determined by ELISA, and IR was estimated using the homeostasis model assessment IR index (HOMA-IR).ResultsAfter controlling for BMI status, levels of both total and HMW adiponectin were significantly lower in women with PCOS compared with normal women (P<0.05). Furthermore, HMW adiponectin provided a stronger contribution to models predicting IR than total adiponectin. Lastly, decreased HMW adiponectin was associated with increased HOMA-IR in both normal and PCOS women, and this association was independent of both overall adiposity and visceral adiposity.ConclusionLevels of both total and HMW adiponectin were decreased in Chinese women with PCOS compared with normal control women, and the differences in HMW adiponectin persisted after controlling for BMI. Furthermore, HMW adiponectin is a stronger predictor of IR than total adiponectin in both women with PCOS and normal women.


2007 ◽  
Vol 157 (5) ◽  
pp. 669-676 ◽  
Author(s):  
Susanne Tan ◽  
Susanne Hahn ◽  
Sven Benson ◽  
Tiina Dietz ◽  
Harald Lahner ◽  
...  

AbstractObjectiveInsulin resistance (IR) and obesity are common features of the polycystic ovary syndrome (PCOS). Insulin-sensitizing agents have been shown to improve both reproductive and metabolic aspects of PCOS, but it remains unclear whether it is also beneficial in lean patients without pre-treatment IR. The aim of this study was to determine the influence of metformin on the clinical and biochemical parameters of PCOS irrespective of the presence of basal obesity and IR.DesignThe effect of 6 months of metformin treatment was prospectively assessed in 188 PCOS patients, divided into three groups according to body mass index (BMI; lean: BMI<25 kg/m2, overweight: BMI 25–29 kg/m2, and obese: BMI≥30 kg/m2). Outcome parameters, which were also assessed in 102 healthy controls, included body weight, homeostasis model assessment for IR (HOMA-IR), fasting glucose and insulin levels, area under the curve of insulin response (AUCI), hyperandrogenism, and menstrual irregularities.ResultsIn comparison with the respective BMI-appropriate control groups, only obese but not lean and overweight PCOS patients showed differences in fasting insulin and HOMA-IR. Metformin therapy significantly improved all outcome parameters except fasting glucose levels. Subgroup analyses revealed that in the group of lean PCOS patients without pre-treatment IR, metformin significantly improved HOMA-IR (1.7±1.0 vs 1.1±0.7 μmol/l×mmol/l2) and fasting insulin levels (7.7±4.2 vs 5.4±3.9 mU/l), in addition to testosterone levels (2.6±0.9 vs 1.8±0.7 nmol/l), anovulation rate (2.3 vs 59.5%), and acne (31.8 vs 11.6%; all P<0.017). In the overweight and obese PCOS groups, metformin also showed the expected beneficial effects.ConclusionMetformin improves parameters of IR, hyperandrogenemia, anovulation, and acne in PCOS irrespective of pre-treatment IR or obesity.


2017 ◽  
Vol 29 (4) ◽  
pp. 670 ◽  
Author(s):  
F. Ramezani Tehrani ◽  
M. Zarkesh ◽  
M. Tohidi ◽  
F. Azizi ◽  
A. Zadeh-Vakili

Polycystic ovary syndrome (PCOS) is frequently accompanied by insulin resistance (IR). The aim of the present study was to investigate whether the genetic association between insulin resistance and two single nucleotide polymorphisms (SNPs), namely rs7903146 (C/T) in transcription factor 7-like 2 (TCF7L2) and rs1111875 (A/G) in haematopoietically expressed homeobox (HHEX), is affected by PCOS status in Iranian women. The study participants consisted of 582 women with PCOS (cases) referred to the Reproductive Endocrinology Research Center and 504 subjects without PCOS (controls), randomly selected from the Tehran Lipid and Glucose Study. Cases and controls were further subdivided to two groups according to IR status: those with and without IR. IR was identified on the basis of homeostasis model assessment of insulin resistance (HOMA-IR) ≥2.63. The SNPs in TCF7L2 and HHEX were genotyped by polymerase chain reaction–restriction fragment length polymorphism. There were no significant differences in the distribution of genotypes and alleles between cases and controls (P < 0.05). Among cases, the prevalence of the CC, CT and TT genotypes was 37.8%, 46.3% and 15.9%, respectively, whereas the prevalence of the AA, AG and GG genotypes was 13.5%, 46.1% and 40.4%, respectively. In the control group, the prevalence of the CC, CT and TT genotypes was 32.2%, 53.9% and 13.9%, respectively, whereas the prevalence of the AA, AG and GG genotypes was 11.3%, 48.6% and 40.0%, respectively. After adjustment for age and body mass index, the probability of IR was decreased by 49% among carriers of the A allele in the control group (95% confidence interval 0.33–0.78; P = 0.002). The findings of the present study suggest that the association between IR and diabetogenic polymorphisms may be affected by PCOS status.


2017 ◽  
Vol 14 (4) ◽  
pp. 299-307 ◽  
Author(s):  
Xiaoyu Tu ◽  
Chuanning Yu ◽  
Minzhi Gao ◽  
Yu Zhang ◽  
Zhaofeng Zhang ◽  
...  

2010 ◽  
Vol 163 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Valentina Chiavaroli ◽  
Marco Liberati ◽  
Francesco D'Antonio ◽  
Fabio Masuccio ◽  
Rita Capanna ◽  
...  

ObjectiveGNRH analog (GNRHa) therapy has not been supported by beneficial effects on adult stature in girls with early puberty. Furthermore, an increased prevalence of polycystic ovary syndrome (PCOS) has been described in girls treated for central precocious puberty. Women with PCOS are at increased risk of cardiometabolic dysfunctions and infertility. Our aim was to assess GNRHa effectiveness on reaching adult stature and the risk of PCOS in girls with early puberty.DesignLongitudinal study of GNRHa-treated and GNRHa-untreated girls at baseline and at final height.MethodsTwenty-five GNRHa-treated girls and 55 controls were compared. Insulin resistance (IR; homeostasis model assessment of IR (HOMA-IR) and glucose-to-insulin ratio (G/I)), the effect of GNRHa on final height, and the prevalence of PCOS were assessed.ResultsIn GNRHa-treated girls, no significant difference was found between predicted final height and final height, whereas a significant difference was detected in untreated girls (P=0.0001). At final height, GNRHa-treated girls showed higher HOMA-IR and lower G/I (P=0.03 for both) as well as higher DHEAS and androstenedione levels (P=0.02 and P=0.01 respectively) than untreated girls. The prevalence of PCOS and hyperandrogenemia was significantly higher in GNRHa-treated adolescents than in untreated adolescents (36 and 14.5% respectively, P=0.04; 56 and 23.6% respectively, P=0.01). Finally, gonadotropin-suppressive therapy was significantly related to PCOS during adolescence (P=0.03).ConclusionsIn girls with early puberty, GNRHa therapy is associated with the achievement of predicted final height; nevertheless, this treatment seems to act as an independent risk factor for the development of PCOS already during adolescence.


2007 ◽  
Vol 92 (11) ◽  
pp. 4191-4198 ◽  
Author(s):  
Margrit Urbanek ◽  
Susan Sam ◽  
Richard S. Legro ◽  
Andrea Dunaif

Abstract Context: Polycystic ovary syndrome (PCOS), the most common reproductive endocrine disorder of premenopausal women, is also associated with metabolic abnormalities including insulin resistance and an increased risk for diabetes mellitus. We previously mapped a PCOS susceptibility locus to chromosome 19p13.2 near the dinucleotide repeat marker D19S884. Objective: Our objective is to localize the chromosome 19p13.2 PCOS susceptibility locus and determine its impact on metabolic features of PCOS. Design: Resequencing and family-based association testing were used to examine the effect of sequence variation within 100 kb of D19S884 on the reproductive and metabolic phenotypes of PCOS. Setting: The study was conducted in an academic medical center. Subjects: Genetic analyses were performed on DNA obtained from1723 individuals in 412 families with 412 index cases and 43 affected sisters of predominantly European origin (&gt;94%). Genotype-phenotype associations were assessed in 601 women with PCOS and 168 brothers of affected women. Results: D19S884 allele 8 (A8) within intron 55 of the fibrillin-3 (FBN3) gene showed the strongest evidence for association with PCOS of 53 variants tested (Pcorrected = 0.0037). A8 was also associated with higher levels of fasting insulin and homeostasis model assessment for insulin resistance in women with PCOS and higher fasting levels of proinsulin and proinsulin/insulin ratio in brothers. Conclusions: These findings strongly suggest that A8 of D19S884 is the chromosome 19p13.2 PCOS susceptibility locus. The association of D19S884 with markers of insulin resistance and pancreatic β-cell dysfunction suggests that the same variant contributes to the reproductive and metabolic abnormalities of PCOS in affected women and their brothers.


2013 ◽  
Vol 169 (5) ◽  
pp. 569-576 ◽  
Author(s):  
Ramon Bossardi Ramos ◽  
Denusa Wiltgen ◽  
Poli Mara Spritzer

ObjectiveTo assess whetherTCF7L2single nucleotide polymorphisms rs7903146 C/T and rs11196236 C/T are associated with polycystic ovary syndrome (PCOS) in South Brazilian women.DesignCross-sectional study.MethodsTwo hundred PCOS patients and 102 non-hirsute, ovulatory controls were genotyped by real-time PCR. Haplotypes were constructed from the combination of both polymorphisms. Frequencies were inferred using the PHASE 2.1.1 software.Results and conclusionsThe distribution of rs7903146 (PCOS, 54.4% CC; 28.5% CT; 17.1% TT; controls, 51.0% CC; 37.0% CT; 12.0% TT) and rs11196236 (PCOS, 4.3% CC; 33.5% CT; 62.2% TT; controls, 3.2% CC; 35.5% CT; 61.3% TT) was similar between the groups. rs7903146 and rs11196236 were not in linkage disequilibrium (|D′|=0.34;r2=0.07). PCOS participants were younger, with higher age-adjusted BMI, waist circumference, blood pressure, triglycerides, insulin, homeostasis model assessment index to estimate insulin resistance and total testosterone, and lower HDL-C and sex hormone binding globulin vs controls. In PCOS, no differences between genotypes and haplotypes were found for clinical and metabolic variables. However, for each T (rs7903146) and T (rs11196236) allele added to the haplotypes, a variation of 5.87 cm in waist (Ptrend=0.01), 10.7 mg/dl in total cholesterol (Ptrend=0.03), and 10.3 mg/dl in LDL-C (Ptrend=0.01) was recorded.TCF7L2variants are probably not implicated in PCOS development in South Brazilian women.


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