Common variant rs7597774 in ADD2 is associated with dilated cardiomyopathy in Chinese Han population

Int J Clin Exp Med. 2015 Jan 15;8(1):1188-96. eCollection 2015.

Abstract

Two polymorphisms, rs7597774 and rs1739843 in ADD2 and HSPB7 respectively, were found to be associated with dilated cardiomyopathy (DCM) in European cohorts but the results were not validated in the Chinese Han population. We aimed to test the association of the two variants with DCM in a cohort of Chinese Han population. DCM (399) and control (1384) individuals were identified from the GeneID database in China, and DNA was isolated from peripheral blood lymphocytes for genotyping. Alleles were amplified by PCR, and amplicons harboring polymorphisms rs1739843 and rs7597774 were directly genotyped using high-resolution melting analysis. Statistical analysis was subsequently performed to evaluate the association of the variants with DCM. Allelic analysis demonstrated that rs7597774 was significantly related to DCM (P -adj = 0.0157), and an increased risk of DCM was specifically associated with the minor allele A (OR = 1.582). High-grade cardiac dysfunction (NYHA III/IV) was a clinical parameter significantly associated with the rs7597774 genotypes AA + AC relative to genotype CC (P = 0.021). Furthermore, DCM patients with the rs7597774 genotype AA tended to undergo more invasive medical interventions than those with the genotype CC (P = 0.008). No association was detected between rs1739843 and DCM under any allelic (P -adj = 0.407, OR = 0.920) or genotypic model. In the Chinese Han population, rs7597774 but not rs1739843 was found to be associated with DCM. This study is the first to demonstrate that underlying genotypes of rs7597774 may assist in assessing the heart functional status of DCM patients and also in the prediction of the benefit of particular therapies for these patients.

Keywords: ADD2; HSPB7; NYHA heart functional classification; dilated cardiomyopathy; polymorphisms; therapeutic regimens.