title: Association of KCTD10, MVK, and MMAB polymorphisms with dyslipidemia and coronary heart disease in Han Chinese population.
abstract: BACKGROUND
  Several genome-wide association studies have discovered novel loci at chromosome 12q24, which includes mevalonate kinase (MVK), methylmalonic aciduria (cobalamin deficiency) cbIB type (MMAB), and potassium channel tetramerization domain-containing 10 (KCTD10), all of which influence HDL-cholesterol concentrations. However, there are few reports on the associations between these polymorphisms and HDL-C concentrations in Chinese population. This study aimed to evaluate the associations between functional polymorphisms in three genes (MVK, MMAB and KCTD10) and HDL-C concentrations, as well as coronary heart disease (CHD) susceptibility in Chinese individuals.
  
  
  METHODS
  We systematically selected and genotyped 18 potentially functional polymorphisms in MVK, MMAB and KCTD10 by using the TaqMan OpenArray Genotyping System in a Chinese population including 399 dyslipidemia cases, 697 CHD cases and 465 controls. Multivariate logistic regression analyses were performed to estimate the relationship between the genotypes and dyslipidemia, CHD risk with adjustment of relevant confounders.
  
  
  RESULTS
  Among six polymorphisms showing significant associations with dyslipidemia, the minor alleles of rs11066782 in KCTD10, rs11613718 in KCTD10 and rs11067233 in MMAB were significantly associated with a decreased risk of CHD (additive model: OR = 0.71, 95 % CI = 0.53-0.97, P = 0.029 for rs11066782; OR = 0.73, 95 % CI = 0.54-0.99, P = 0.044 for rs11613718 and OR = 0.57, 95 % CI = 0.40-0.80, P = 0.001 for rs11067233). Further combined analysis showed that individuals carrying "3-4" favorable alleles presented a 62 % (OR = 0.38, 95 % CI = 0.21-0.66) decreased risk of CHD compared with those carrying "0-2" favorable alleles.
  
  
  CONCLUSIONS
  These findings suggest that rs11066782 in KCTD10, rs11613718 in KCTD10 and rs11067233 in MMAB may contribute to the susceptibility of CHD by altering plasma HDL-C levels in Han Chinese.
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, 101 Longmian AV., Nanjing, Jiangsu, 211166, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Chronic Non-communicable Disease Control, Wuxi Center for Disease Control and Prevention, Wuxi, 214023, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, 101 Longmian AV., Nanjing, Jiangsu, 211166, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, 101 Longmian AV., Nanjing, Jiangsu, 211166, China.
authors.forename: Jiaping
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, 101 Longmian AV., Nanjing, Jiangsu, 211166, China.
authors.forename: Juncheng
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, 101 Longmian AV., Nanjing, Jiangsu, 211166, China.
authors.forename: Guangfu
authors.initials: G
authors.lastname: Jin
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, 101 Longmian AV., Nanjing, Jiangsu, 211166, China.|Department of Social Medicine and Health Education, School of Public Health, Nanjing Medical University, 101 Longmian AV., Nanjing, Jiangsu, 211166, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, 101 Longmian AV., Nanjing, Jiangsu, 211166, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, 101 Longmian AV., Nanjing, Jiangsu, 211166, China. sjliu@njmu.edu.cn.|Department of Social Medicine and Health Education, School of Public Health, Nanjing Medical University, 101 Longmian AV., Nanjing, Jiangsu, 211166, China. sjliu@njmu.edu.cn.
authors.forename: Sijun
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, 101 Longmian AV., Nanjing, Jiangsu, 211166, China. sc100@126.com.
authors.forename: Chong
authors.initials: C
authors.lastname: Shen
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, 101 Longmian AV., Nanjing, Jiangsu, 211166, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
mesh_terms: D000328:Adult; D000368:Aged; D019883:Alkyl and Aryl Transferases / Q000235:genetics*; D000483:Alleles; D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics; D003327:Coronary Disease / Q000235:genetics* / Q000473:pathology; D050171:Dyslipidemias / Q000235:genetics* / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics*
chemical_list: D008076:Cholesterol, HDL; C539187:KCTD10 protein, human; D024642:Potassium Channels, Voltage-Gated; D019883:Alkyl and Aryl Transferases; C019920:cob(I)alamin adenosyltransferase; D017853:Phosphotransferases (Alcohol Group Acceptor); C021796:mevalonate kinase
keywords: Coronary heart disease; HDL-C; KCTD10; MMAB; MVK