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B. Fan, D.Y. Wang, D.T. L. Liu, W.C. Ko, W.M. Chan, D.S. C. Lam, C.P. Pang; Interaction Analysis of CYBA and RAGE Gene Polymorphisms in Diabetic Retinopathy Patients . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1725.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetic retinopathy (DR) is a sight–threatening complication of microvasculature for diabetes mellitus. It can be categorised into proliferative DR (PDR) and non–proliferative DR (NPDR). The NADPH oxidase p22phox (CYBA) gene C242T polymorphism was associated with vascular superoxide production in human blood vessels from patients with coronary artery disease. The receptor for advanced glycation end products (RAGE) gene G1704T polymorphism was associated with microvascular dermatoses and antioxidant status. An interactive effect of CYBA–C242T and RAGE–G1704T was found in development of diabetic nephropathy, another microvascular complication of similar pathogenesis as DR. It is thus worthy to investigate whether there are similar interactive effects of these gene polymorphisms on DR. This study was designed to investigate the possible interactive effects of the CYBA–C242T and RAGE–G1704T gene polymorphisms on the development of DR.
We carried out an association study involving 554 unrelated subjects with diabetes mellitus, including 120 (21.7%) PDR, 208 (37.5%) NPDR and 226 (40.8%) patients without DR. Genotypes of the gene polymorphisms were determined by polymerase chain reaction followed by restriction endonuclease assays. Chi–square test or Fisher’s exact test was used to compare the genotype frequencies between patient groups. Logistic regression analysis was applied to explore gene–gene interactions.
The genotype frequencies of CYBA–C242T and RAGE–G1704T were not different between patients with PDR or NPDR and controls without DR (P = 0.23 and 0.25 respectively). However, a significant interactive effect was identified between the two polymorphisms on DR (P = 0.036). After adjusting for sex, hypertension, triglycerides, non–HDL cholesterol and BMI, the interaction effect appeared more significant (P = 0.0004).
The CYBA–C242T and RAGE–G1704T gene polymorphisms interactively contribute to the development of DR. Our findings suggest that assessment of the combination of these two polymorphisms may be useful in identifying the risk for developing DR.
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