title: The D allele of the ACE I/D common gene variant is associated with Type 2 diabetes mellitus in Caucasian subjects.
abstract: The deletion D allele of the angiotensin-I converting enzyme (ACE) I/D gene variant is associated with higher ACE activity in Caucasians and previous studies in non-Caucasian samples have suggested an association between the D allele and type 2 diabetes (Type 2DM). The aim of this study was to compare the genotype distribution between Caucasian subjects with Type 2DM and non-diabetic Caucasian men. Genotype distribution was compared between 574 Caucasian subjects with Type 2DM, recruited from the UCL Diabetes and Cardiovascular Disease Study and 2413 non-diabetic Caucasian men, recruited from the second Northwick Park Heart Study. Within both samples, genotype distributions were in Hardy-Weinberg equilibrium. The genotype distributions in those with Type 2DM compared to the non-diabetic men (II/ID/DD) was 18%/50%/32% vs. 23%/49%/27%, p=0.004. In accordance with this, the frequency of the D allele was higher in those with Type 2DM (0.574 [0.55-0.60] vs. 0.519 [0.50-0.53], p=0.001). On combining the two samples, the odds ratio (OR) for Type 2DM was significantly higher in D allele carriers compared to II subjects (OR=1.55, p=0.02, after adjustment for age, sex, BMI, blood pressure, and lipids). In those with diabetes, there was a significant association between genotype and a family history of diabetes. The odds ratio for a family history of diabetes in DD compared to II subjects was 1.52 [0.89-2.60], p=0.03. This study clearly shows an association between the ACE I/D common gene variant and Type 2DM.
authors.affiliation: Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free and University College London Medical School, 5 University Street, London WC1E 6JF, United Kingdom. rmhajst@ucl.ac.uk
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Stephens
authors.forename: Sukhbir S
authors.initials: SS
authors.lastname: Dhamrait
authors.forename: Jaqueline A
authors.initials: JA
authors.lastname: Cooper
authors.forename: Jayshree
authors.initials: J
authors.lastname: Acharya
authors.forename: George J
authors.initials: GJ
authors.lastname: Miller
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Hurel
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
mesh_terms: D000483:Alleles; D000704:Analysis of Variance; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D008297:Male; D016017:Odds Ratio; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D006113:United Kingdom; D044465:White People
chemical_list: C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A