title: [Association between single nucleotide polymorphism of rs2252673 of INSR gene and polycystic ovarian syndrome].
abstract: OBJECTIVE
  This study is designed to determine whether an association exists between single nucleotide polymorphism (SNP) variant rs2252673 of insulin receptor (INSR) gene and polycystic ovarian syndrome (PCOS) in Han Chinese in order to identify INSR as a genetic susceptibility factor for PCOS.
  
  
  METHODS
  A total of 224 women with PCOS, 192 controls and 672 participants consisting of 224 trios (mother, father and offspring with PCOS) were recruited from the Hospital for Reproductive Medicine Affiliated to Shandong University, from July 2007 to April 2013. Genomic DNA was extracted according to the manufacturer's protocol. SNP rs2252673 of INSR gene was amplified by PCR and then sequenced on an automated sequencer. Moreover, clinical and metabolic features of the patients with PCOS were compared according to the genotypes. The subjects were divided into twot groups according to body mass index (BMI), and then the results were compared between two groups. And the transmitted disequilibrium test (TDT) was applied for data analysis.
  
  
  RESULTS
  (1) There were three kinds of genotype of CC, CG and GG. Genotype frequencies of rs2252673 were 8.0%, 38.8%, 53.1% and 14.6%, 42.2%, 43.2% in the PCOS group and the control group, respectively. The allele frequencies of C and G were 27.5%, 72.5% and 35.7%, 64.3% in the PCOS group and the control group, respectively. There were statistical differences in genotype frequencies and allele frequencies between two groups (all P < 0.05 ). (2)No significant differences were observed in the different genotype according to clinical and metabolic characteristics of women with PCOS(P > 0.05). But when merging the genotype CG and GG, carriers of the CG and GG genotypes in women with PCOS were slightly associated with total cholesterol (TC) levels (t = 2.072, P = 0.048) and lower high-density lipoprotein (HDL) levels (t = 2.274, P = 0.026). Although statistical significance was not achieved, there was an increased tendency in fasting blood glucose (FBG) and fasting insulin (FINS) levels in CG and GG genotypes in PCOS cases.(3)Between the obesity and the non-obesity with PCOS, there was no statistical significance in the genotype and allele frequencies (χ(2) = 0.054, P = 0.974; χ(2) = 0.022, P = 0.883 ). (4) The results of families based analysis shown that genotype distribution of the SNP rs2252673 was in Hardy-Weinberg equilibrium (P > 0.05). After the TDT, the G allele in SNP rs2252673 was over transmitted in families (transmitted:non-transmitted = 120:88; χ(2) = 4.923, P = 0.027). There was a transmitted disequilibrium in rs2252673, which implies the association of INSR and PCOS were independent of population stratification.
  
  
  CONCLUSIONS
  There were a association between the SNP variant rs2252673 of INSR gene and the susceptibility to PCOS in Han Chinese women, which was independently of body mass index. The carrier of G allele frequency of rs2252673 may have higher risk of PCOS.
authors.affiliation: Hospital for Reproductive Medicine Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Du
authors.forename: Ze
authors.initials: Z
authors.lastname: Wang
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Zhang
authors.forename: Lili
authors.initials: L
authors.lastname: Jia
authors.forename: Fengli
authors.initials: F
authors.lastname: Zhang
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Email: chenzijiang@vip.163.com.
authors.forename: Zijiang
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000483:Alleles; D054458:Amplified Fragment Length Polymorphism Analysis; D015703:Antigens, CD / Q000235:genetics*; D015992:Body Mass Index; D016022:Case-Control Studies; D002681:China; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007328:Insulin; D007333:Insulin Resistance; D008075:Lipoproteins, HDL; D009765:Obesity; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011972:Receptor, Insulin / Q000235:genetics*
chemical_list: D015703:Antigens, CD; D007328:Insulin; D008075:Lipoproteins, HDL; D011972:Receptor, Insulin