A common variant in the ACE gene is associated with peripheral neuropathy in women with type 2 diabetes mellitus.
OBJECTIVE
The D allele of the ACE I/D gene variant is associated with higher tissue and serum ACE activity. Previously, studies have suggested an association between the D allele with the microvascular complications of diabetes. The aim of this study was to explore the impact of this genotype in relation to clinically manifest peripheral neuropathy (PN) in a cohort of subjects with type 2 diabetes mellitus (type 2 DM).


METHODS
Five hundred and seventy-two Caucasian subjects (230 females, 342 males) with type 2 DM were recruited from the diabetes clinic at University College London Hospitals NHS Trust. Clinically manifest PN was determined from a standardized clinical examination.


RESULTS
The ACE I/D genotype distribution was in Hardy-Weinberg equilibrium. In the whole group, no significant association was seen between genotype and PN; however, when stratified by sex, the D allele was associated with PN in females but not in males. The odds ratio (OR) for PN in the D allele carriers compared to those homozygous for the I allele was significantly higher in females [OR 2.93 (1.09-7.63), P=.027] but not in males [OR 1.2 (0.61-2.36), P=.60].


CONCLUSIONS
The presence of the D allele is associated with increased risk of peripheral neuropathy in females but not in male subjects with type 2 DM, suggesting a role for the renin-angiotensin system in the development of PN.
Stephens
Jeffrey W
JW
Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free and University College London Medical School, London WC1E 6JF, UK. jeffrey.stephens@swansea-tr.wales.nhs.uk
Dhamrait
Sukhbir S
SS
Acharya
Jayshree
J
Humphries
Steve E
SE
Hurel
Steven J
SJ
D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003929:Diabetic Neuropathies / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D012737:Sex Factors
D007703:Peptidyl-Dipeptidase A