Macrovascular and microvacular changes in diabetes mellitus type 1 are modified by the gene for connexin 37 in men but not in women

Abstract

Abstract Introduction Diabetes mellitus type 1 (DMT1) is a strong risk factor for macrovascular and microvascular disease. These vascular pathologies can be strongly modified by genetic factors. One of intensively investigated candidate genes is the gene for connexin37 (Cx37) (C1019>T (Pro319>Ser). The role of this gene in cardiovascular disease and diabetes mellitus had been already described in several different populations, but not in patients with DMT1. Purpose To determine whether the presence of macrovascular and microvascular changes is modified by Cx37 gene polymorphism in middle aged men and women diagnosed with DMT1 of similar age and with similar duration of DMT1. Methods In 253 men (mean age 43.0±14.5 years; mean duration of diabetes 22.6±14.0 years) and 245 women (mean age 43.9±12.9 years; mean duration of diabetes 21.3±10.5 years) macrovascular disease was measured by duplex B-Mode ultrasound and classified as Belcaro score (1–4) in carotid and femoral arteries. Microvascular disease was assessed by the presence of retinopathy, nephropathy, neuropathy and diabetic foot. Cx37 gene polymorphism was established by PCR. Results In men, in CC homozygotes we observed more advanced macrovascular changes in carotid arteries (Belcaro score more than 2) than in CT heterozygotes/TT homozygotes (7.5 vs. 15.2%; p=0.031). No significant differences were found in changes of carotid arteries in women and in changes of femoral arteries both in men and women. Regarding microvascular changes, in men, in CC homozygotes, the diabetic foot was diagnosed more frequently than in CT heterozygotes/TT homozygotes (7.4 vs. 16.1%; p=0.046). No significant differences were found in women and in other types of microvascular disease both in men and women. Conclusion These results indicate that macrovascular and microvascular changes in DMT1 can be modified by Cx37 gene polymorphism in men, but not in women. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by the Ministry of Health of the Czech Republic, grant No. NU20-01-00083 and by Ministry of Health of the Czech Republic under its conceptual development of the research organization program (Institute for Clinical and Experimental Medicine–IKEM, IN 00023001. All rights reserved.