title: Genetic variant of the renin-angiotensin system and prevalence of type 2 diabetes mellitus: a modest but significant effect of aldosterone synthase.
abstract: Recent genome-wide association studies have identified multiple variants that confer risk of type 2 diabetes mellitus (DM). However, established associations explain only a part of the heritability. Thus, even at the genome-wide association studies era, candidate gene approach should be still useful. Recent interventional studies against the renin-angiotensin system (RAS) showed reduction in new onset of DM, implying the system is involved in the onset. We substantiated the hypothesis that genetic variants of RAS have significant association with prevalence of DM. We enrolled to the study consecutive 782 subjects who had consulted our hospitals for mainly lifestyle related diseases. They consisted of 282 (36.1 %) diabetes cases. Genotypes were assayed with genomic DNA for conventional four genes of the RAS, i.e., angiotensin converting enzyme (ACE) insertion/deletion variant, angiotensinogen (AGT) M235T variant, angiotensin II type I receptor (AT1) A1166C variant, and aldosterone synthase (CYP11B2) C-344T variant. Association between the genetic variants of the RAS and prevalence of type 2 DM was tested. A significant association of DM and CYP11B2 genotype was obtained. There was no significant association between DM and ACE, AGT and AT1 variants. A multivariate logistic regression showed that age, gender, and CYP11B2 genotype were independent factors for association to diabetes, the DM risk of CC/CT to TT being 1.40 (95 % CI 1.04-1.90, p = 0.029). Thus, it is concluded that a genetic variant of the RAS should have a modest but significant impact on the onset of type 2 diabetes mellitus.
authors.affiliation: Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, 23-3, Matsuokashimoaizuki, Eiheiji, Fukui, 910-1193, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Ichikawa
authors.forename: Tadashi
authors.initials: T
authors.lastname: Konoshita
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakaya
authors.forename: Katsushi
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Mika
authors.initials: M
authors.lastname: Yamada
authors.forename: Satsuki
authors.initials: S
authors.lastname: Sato
authors.forename: Michiko
authors.initials: M
authors.lastname: Imagawa
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Makino
authors.forename: Miki
authors.initials: M
authors.lastname: Fujii
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Zenimaru
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Arakawa
authors.forename: Jinya
authors.initials: J
authors.lastname: Suzuki
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Ishizuka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000808:Angiotensinogen / Q000235:genetics; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D012084:Renin-Angiotensin System
chemical_list: D000808:Angiotensinogen; D019405:Cytochrome P-450 CYP11B2; D007703:Peptidyl-Dipeptidase A