Discovery of the connection among age-related macular degeneration, MTHFR C677T and PAI 1 4G/5G gene polymorphisms, and body mass index by means of Bayesian inference methods

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly. The aim of this study was therefore to explore the relationship between the presence of multiple gene polymorphisms and 2 distinct advanced 'dry and wet' AMD phenotypes, and to assess gene interactions with the inuence of personal factors in a Turkish population as a pilot study. For the analysis, the data were collected from 73 unrelated participants, grouped as 29 wet and 26 dry AMD patients, and 18 healthy controls. They were all genotyped for the multiple gene polymorphisms in 12 dierent genes. The data set collected was then analyzed using the Bayesian inference methods and visualized by means of the Bayesian networks. The results suggest that: 1) the PAI-1 4G/5G and FV G1691A genes have joint roles in the separation of the 3 groups; 2) both wet and dry AMD can be separated from the control group using the genes PAI-1 4G/5G, FV G1691A, FXII V34L, and PT G20210A; 3) although the wet AMD and control groups can be separated by the combination of the ACE I=D and B-brinogen-455 G-A gene polymorphisms, there seems to be no signicant eect of the genes on the separation between the dry AMD and control groups; 4) the wet AMD and control groups can be distinguished by the combination of body mass index and the MTHFR-C677T and PAI-1 genes; and 5) there is a correlation between wet AMD and a high body mass index (>30 kg/m 2 ). It was also found that the impact of body mass index on the disease development seems only in question with the connective availability of the genes MTHFR C677T and PAI-1. It can be concluded that the combination of the MTHFR C677T and PAI-1 4G/5G gene polymorphisms in the presence of obesity may increase the risk of wet AMD. In addition, the results further support a complex interplay among genetic and environmental factors in the development of dierent phenotypes.