Association of angiotensin-converting enzyme gene promoter single nucleotide polymorphisms and haplotype with major depression in a northeastern Thai population

Abstract

Introduction: Angiotensin-converting enzyme (ACE) is thought to influence the activity of the hypothalamic-pituitary-adrenocortical system, which shows hyperactivity in the majority of patients with major depressive disorder (MDD). This study aimed at determining an association between two single nucleotide polymorphisms (SNPs) (rs4291;-240A/T and rs4292;-93T/C) of the ACE gene promoter and MDD in northeastern Thais. Subjects and methods. In the present case-control study, genotyping of 187 unrelated patients with MDD (44.89+/-12.92 years) and 207 unrelated healthy controls (41.34+/-9.76 years) from the northeastern part of Thailand was performed using polymerase chain reaction-restriction fragment length polymorphism technique. Results: Comparing the two groups, no significant difference was observed with regard to either genotype distributions or allele frequencies of the -93T/C SNP of ACE. For the -240A/T SNP, a significant difference in genotype distributions was found (chi(2)=6.65, df=2, p=0.036).The presence of the -240A allele of ACE was associated with a decreased risk for MDD compared with the -240T allele (chi(2)=4.24, df=1, p=0.040, odds ratio=0.702 [95% confidence interval=0.508-0.971]). Moreover, haplotype frequency analysis revealed that the -240T/-93T combination was significantly over-represented in patients with MDD in comparison with controls (13.6% and 6.8%, p=0.002 on chi(2) test, empirical p=0.004). Conclusions: In the present investigation, an association between the -240A allele and a reduced risk for MDD was observed, but the genotype distributions of controls were only just in marginal agreement with Hardy-Weinberg equilibrium. The T-T haplotype in the ACE gene was significantly associated with an increased risk for MDD.