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

Department of Clinicals Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand

Thapanut Sritharathikhun

Loei Rajanagarindra Psychiatric Hospital, Loei 42000, Thailand

Sarawut Suttirat

Faculty of Medical Technology, Huachiew Chalermprakiet University, Samut Prakan 10540, Thailand

Tewin Tencomnao

Department of Clinicals Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand, tewin.t{at}chula.ac.th

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 (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 (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 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.

Key Words: angiotensin-converting enzyme • association study • genetic polymorphism • major depression • Thai population

Journal of Renin-Angiotensin-Aldosterone System, Vol. 10, No. 3, 179-184 (2009)
DOI: 10.1177/1470320309344151


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