Common Variants in the ARG1 Gene Contribute to the Risk of Dilated Cardiomyopathy in the Han Chinese Population.

Background: Arginase I, encoded by the ARG1 gene, is an enzyme that catalyzes the conversion of arginine to ornithine in the urea cycle; mutations in this gene has recently been reported to be associated with dilated cardiomyopathy (DCM) in Pakistan. The present study aimed to investigate the relationship between ARG1 gene mutations and DCM in the Han Chinese population. Methods: A total of 488 DCM cases and 924 matched-healthy controls were recruited. All subjects were genotyped for 12 tag single nucleotide polymorphisms (SNPs) within the ARG1 gene. Genetic association studies, including SNP and haplotype analyses, were performed. Further analyses were conducted to examine the correlations between the associated SNPs and specific clinical characteristics. Results: Only the rs2781666 and rs2781667 loci in the ARG1 gene were found to be significantly associated with DCM compared to the healthy controls. The risk of DCM at both of these loci for T allele carriers was ∼1.42-fold higher than that for carriers of the alternative alleles. There were significant differences in end-diastolic interventricular septal diameter, end-diastolic left ventricular posterior wall diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and left ventricular ejection fraction among the genotype distributions of both SNPs. Furthermore, we found that the T alleles at the rs2781666 and rs2781667 loci were significantly associated with DCM in gender subgroups and the subgroup of patients <58 years of age. The haplotype T-T (rs2781666-rs2781667) also showed a significant association with DCM. Conclusion: Our results support the hypothesis that alleles and haplotypes of the ARG1 gene are significantly involved in the etiology of DCM in the Han Chinese population, but further research is necessary to elucidate the mechanism governing this association.