title: Study of Five Pubertal Transition-Related Gene Polymorphisms as Risk Factors for Premature Coronary Artery Disease in a Chinese Han Population.
abstract: BACKGROUND
  Recently, single nucleotide polymorphisms (SNPs) (DLK-rs10144321, SIX6-rs1254337, MKRN3-rs12148769, LIN28B-rs7759938, and KCNK9-rs1469039) were found to be strongly associated with age at menarche. Recent studies also suggested that age at menarche is a heritable trait and is associated with risks for obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease, and all-cause mortality. Since an association between these five SNPs and premature coronary artery disease (CAD) has never been reported, we investigated whether these SNPs are associated with premature CAD and its severity in a Chinese Han population.
  
  
  METHODS
  We enrolled 432 consecutive patients including 198 with premature CAD (<55 years in men and <65 years in women) and 234 controls. All subjects were genotyped for the five SNPs by the PCR-ligase detection reaction method. The associations between these SNPs and premature CAD and its severity were analyzed.
  
  
  RESULTS
  The following genotypes were identified: GG, AG, and AA at rs10144321 and rs12148769; TT, AT, and AA at rs1254337; CC, CT, and TT at rs1469039; and TT and CT at rs7759938. Significant differences in genotype distribution frequencies at rs1254337 were found between controls and patients with premature CAD (P<0.05). No associations were found between the five SNPs and the severity of coronary lesions (all P>0.05). Compared with controls, patients with premature CAD had a higher prevalence of T2DM and dyslipidemia, and the proportion of patients with T2DM rose significantly with an increase in the number of stenosed coronary vessels (all P<0.05). After adjustment for the clinical parameters in multivariable analysis, three factors were identified that significantly increased the risk of premature CAD: the AA genotype at rs1254337 (OR: 2.388, 95% CI: 1.190-4.792, P = 0.014), male gender (OR: 1.565, 95% CI: 1.012-2.420, P = 0.044), and T2DM (OR 2.252, 95% CI: 1.233-4.348, P = 0.015).
  
  
  CONCLUSIONS
  Among the five pubertal transition-related gene polymorphisms, we identified an association between rs1254337 and premature CAD in a Chinese Han population.
authors: Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai 200233, China.
authors: Bin
authors: B
authors: Chen
authors: Central Laboratory, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai 200233, China.
authors: Fangyi
authors: F
authors: Xie
authors: Department of Cardiology, The Affiliated Zhongda Hospital of Southeast University, No. 87 Dingjiaqiao, Nanjing 210009, China.
authors: Chengchun
authors: C
authors: Tang
authors: Department of Cardiology, The Affiliated Zhongda Hospital of Southeast University, No. 87 Dingjiaqiao, Nanjing 210009, China.
authors: Genshan
authors: G
authors: Ma
authors: Department of Endocrinology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai 200233, China.
authors: Li
authors: L
authors: Wei
authors: Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai 200233, China.
authors: Zhong
authors: Z
authors: Chen
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011627:Puberty / Q000235:genetics*; D012307:Risk Factors