title: Common Variants in Promoter of ADTRP Associate with Early-Onset Coronary Artery Disease in a Southern Han Chinese Population.
abstract: The first genome-wide association study for coronary artery disease (CAD) in the Han Chinese population, we reported recently, had identified rs6903956 in gene ADTRP on chromosome 6p24.1 as a novel susceptibility locus for CAD. The risk allele of rs6903956 was associated with decreased mRNA expression of ADTRP. To further study the correlation of ADTRP expression and CAD, in this study we evaluated the associations of eight common variants in the expression-regulating regions of ADTRP with CAD in the Southern Han Chinese population. Rs169790 in 3'UTR, rs2076189 in 5'UTR, four SNPs (rs2076188, rs7753407, rs11966356 and rs1018383) in promoter, and two SNPs (rs3734273, rs80355771) in the last intron of ADTRP were genotyped in 1716 CAD patients and 1572 controls. The correlations between these loci and total or early-onset CAD were investigated. None of these loci was discovered to associate with total CAD (P > 0.05). However, with early-onset CAD, significant both allelic and genotypic associations of rs7753407, rs11966356 and rs1018383 were identified, after adjustment for risk factors of age, gender, hypertension, diabetes, lipid profiles and smoking (adjusted P < 0.05). A haplotype AGCG (constructed by rs2076188, rs7753407, rs11966356 and rs1018383) was identified to protect subjects from early-onset CAD (OR = 0.332, 95% CI = 0.105-0.879, adjusted P = 0.010). Real-time quantitative reverse transcription polymerase chain reaction assay showed that the risk alleles of the associated loci were significantly associated with decreased expression of ADTRP mRNA. Moreover, the average level of ADTRP mRNA expression in early-onset CAD cases was significantly lower than that in controls. Our results provide new evidence supporting the association of ADTRP with the pathogenesis of early-onset CAD.
authors.affiliation: Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China; Guangzhou Forensic Science Institute, Guangzhou, Guangdong, China.
authors.forename: Er-Wen
authors.initials: EW
authors.lastname: Huang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Long-Yun
authors.initials: LY
authors.lastname: Peng
authors.affiliation: Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Jin-Xiang
authors.initials: JX
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X Institute, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Guangzhou Forensic Science Institute, Guangzhou, Guangdong, China.
authors.forename: Qu-Yi
authors.initials: QY
authors.lastname: Xu
authors.affiliation: Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Qiu-Ping
authors.initials: QP
authors.lastname: Wu
authors.affiliation: Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Shuang-Bo
authors.initials: SB
authors.lastname: Tang
authors.affiliation: Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Luo
authors.affiliation: Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Shui-Ping
authors.initials: SP
authors.lastname: Liu
authors.affiliation: Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Xiao-Shan
authors.initials: XS
authors.lastname: Liu
authors.affiliation: Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Zhao-Hui
authors.initials: ZH
authors.lastname: Li
authors.affiliation: Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Li
authors.initials: L
authors.lastname: Quan
authors.affiliation: Guangzhou Forensic Science Institute, Guangzhou, Guangdong, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Guangzhou Forensic Science Institute, Guangzhou, Guangdong, China.
authors.forename: He
authors.initials: H
authors.lastname: Shi
authors.affiliation: Guangzhou Forensic Science Institute, Guangzhou, Guangdong, China.
authors.forename: Guo-Li
authors.initials: GL
authors.lastname: Lv
authors.affiliation: Guangzhou Forensic Science Institute, Guangzhou, Guangdong, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Jian-Ding
authors.initials: JD
authors.lastname: Cheng
authors.affiliation: Guangzhou Forensic Science Institute, Guangzhou, Guangdong, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D020121:5' Untranslated Regions / Q000235:genetics; D000368:Aged; D044466:Asian People / Q000208:ethnology* / Q000235:genetics; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; C568706:ADTRP protein, human; D008565:Membrane Proteins