Are Retinal Microvascular Phenotypes Associated With the 1675G/A Polymorphism in the Angiotensin II Type-2 Receptor Gene?

Abstract

The X-linked angiotensin II type-2 receptor (AT2R) gene 1675G/A polymorphism is located in the short intron 1 of the AT2R gene within a sequence motif conforming to a splice branch site. AT2R is expressed in the human retina, but no previous study examined the association between retinal microvascular phenotypes and the AT2R 1675G/A polymorphism. In 340 subjects randomly selected from a Flemish population (mean age, 51.9 years; 51.5% women), we post-processed retinal images using IVAN software to generate the retinal arteriole and venule equivalents (central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE)) and the arteriole-to-venule ratio (AVR). DNA fragments including the AT2R 1675G/A polymorphism were amplified by PCR. We applied a mixed model to assess phenotype-genotype associations while accounting for relatedness and covariables. CRAE, CRVE, and AVR averaged 151.9 µm, 215.2 µm, and 0.710, respectively. CRAE was 5.5 µm greater in women than men and decreased with age (P < 0.05). In multivariable-adjusted analyses, CRAE was higher in hemizygous and homozygous carriers of the AT2R A allele than in their G allele counterparts in both sexes combined (+4.49 µm; P = 0.014) and in men (+4.91 µm; P = 0.032) with a similar trend in women (+3.41 µm; P = 0.14). AVR was increased in the presence of the AT2R A allele compared with AT2R G hemizygotes and homozygotes (+0.024; P = 0.0082). The associations of CRAE and CRVE with other polymorphisms were not significant. Pending confirmation in experimental and epidemiological studies, our findings suggest that diameter of the retinal arterioles might be associated with the AT2R 1675G/A polymorphism.