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.

Highlights

  • Coronary artery disease (CAD) is one of the leading causes of morbidity and mortality worldwide [1, 2]

  • The risk allele A of rs6903956 was discovered to associate with decreased ADTRP mRNA expression, suggesting that low levels of ADTRP expression may be associated with CAD

  • A Genome-wide association studies (GWAS) has revealed that rs6903956 in intron 1 of ADTRP on chromosome 6p24.1 was associated with CAD in a Han Chinese population [13]

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Summary

Introduction

Coronary artery disease (CAD) is one of the leading causes of morbidity and mortality worldwide [1, 2]. It is a complex disease caused by multiple environmental and genetic factors and interactions between them [3, 4]. Linkage analysis and candidate gene association studies have identified several genes involved in the pathogenesis of CAD [5,6,7]. Genome-wide association studies (GWAS) have identified dozens of susceptibility loci for CAD in western populations in the past few years [8,9,10,11,12]. Stronger evidence about the involvement of ADTRP in the pathogenesis of CAD remains to be presented

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