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Ava G Tan, Paul Mitchell, Elena Rochtchina, Annette Kifley, Victoria Flood, Gyungah Jun, Barbara E K Klein, Ching-Yu Cheng, Sudha K Iyengar, Jie Jin Wang; Methylenetetrahydrofolate reductase polymorphisms, serum homocysteine and incident cortical cataract. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):6210.
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Homocysteine has been implicated as a cataractogenic stressor associated with cortical cataract formation. Methylenetetrahydrofolate reductase (MTHFR) gene is known to influence homocysteine levels, in particular the C677T polymorphism. We aimed to assess whether these two factors are associated with incident cortical cataract, and to determine the relationship between MTHFR gene, elevated homocysteine and cortical cataract.
The Blue Mountains Eye Study cohort included 2335 (75.1% of survivors) and 1952 participants (75.6% of survivors) at its second (1997-1999) and third surveys (2002-04), respectively. In this report, the second survey is the baseline and the third survey is the 5-year follow-up when incident cataract was determined. Lens photography was performed and cataract was assessed following the Wisconsin Cataract Grading system. DNA was extracted and serum homocysteine was assessed. Multi-variable adjusted logistic regression models were used to estimate the association between the MTHFR gene and elevated homocyteine on cortical cataract incidence. Path analysis was performed to assess proportion of the genetic association explained by elevated homocysteine.
Elevated homocysteine was associated with a significantly increased risk of cortical cataract after adjusting for age, sex, smoking, hypertension, diabetes, education, myopia and MTHFR 677CT/TT genotype (odds ratio, OR, 1.96, 95% confidence interval, CI, 1.20-3.20). MTHFR 677CT/TT genotypes were significantly associated with incident cortical cataract after adjusting for age, sex, smoking, hypertension, diabetes, education, myopia and homocysteine (OR, 1.71, 95% CI 1.13-2.58). Path analysis showed that the direct association between the MTHFR SNP and incident cortical cataract was OR 1.42 (95% CI 1.07-1.90, beta coefficient 0.35), while the indirect association with cortical cataract via elevated homocysteine was OR 1.19 (95% CI 0.86-1.63, beta coefficient 0.17) (Figure).
Both the MTHFR 677CT/TT polymorphism and elevated homocysteine level significantly increased the risk of incident cortical cataract. One-third of the association between the MTHFR polymorphism and cortical cataract was explained by the influence of homocysteine.
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