ANGIOTENSIN-CONVERTING ENZYME (ACE) INSERTION DELETION (I D) POLYMORPHISM, AND DIABETIC-RETINOPATHY IN SUBJECTS WITH IDDM AND NIDDM/

Angiotensin 1 converting enzyme (ACE) catalyses the step which generat es angiotensin II, and also inactivates bradykinin, peptides which pla y a key role in modulating vascular tone. Plasma ACE levels are under genetic control and up to 50% of the variation is due to an insertion/ deletion (I/D) polymorphism of ACE gene with highest levels found in D D homozygotes. Studies have shown an association of diabetic nephropat hy and ischaemic heart disease with angiotensin converting enzyme gene polymorphism in subjects with diabetes. We examined the association b etween diabetic retinopathy and ACE gene insertion/deletion polymorphi sm in 363 subjects with NIDDM (aged 68.3 +/- 10.7 years; 201 male, 162 female), 186 subjects with IDDM (aged 42.4 +/- 15.0 years; 100 male, 86 female) and 98 controls. These subjects were characterized for ACE I/D polymorphism employing standard primers. Diabetic retinopathy was diagnosed by ophthalmoscopy through dilated pupils by an ophthalmologi st and classified as non-proliferative or proliferative retinopathy. A s expected, diabetic retinopathy was strongly associated with duration of diabetes (p<0.001) in both IDDM and NIDDM. Any retinopathy was pre sent in 51% subjects with IDDM and 49% of subjects with NIDDM, while 2 2% of IDDM subjects and 5% of subjects with NIDDM had proliferative re tinopathy. The frequency of I allele was 0.477 vs 0.482 vs 0.510 and D allele was 0.523 vs 0.518 vs 0.490, among subjects with IDDM, NIDDM a nd controls, respectively. The frequency of ACE I/D genotype was simil ar in subjects with IDDM, NIDDM, and controls (chi(2) = 0.46, df = 4, p = ns). Presence or absence of retinopathy was not significantly asso ciated with ACE genotype in subjects with IDDM (chi(2) = 3.42, df = 2, p = ns) or NIDDM (chi(2) = 0.51, df = 2, p = ns). Among subjects with retinopathy, there was no significant association between ACE genotyp e and type of retinopathy. Controlled for duration of diabetes, the fr equency of I/D genotype was not significantly different in 271 subject s with retinopathy (IDDM and NIDDM combined) when compared with 86 sub jects without retinopathy at 15 years or more after diagnosis of diabe tes (chi(2) = 1.29, df = 2, p = ns). These findings indicate that I/D polymorphism of ACE gene is not a useful marker and is unlikely to pla y a major role in determining genetic susceptibility to diabetic retin opathy or the severity of diabetic retinopathy.