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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.