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Chung-Jung Chiu, Yvette P. Conley, Michael B. Gorin, Gary Gensler, Chao-Qiang Lai, Fu Shang, Allen Taylor; IGF1R Genetic Polymorphisms Affect Risk Of AMD And Predispose Obese People To Higher Risk. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3816.
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Our objective was to investigate if insulin-like growth factor (IGF) axisgenes, together with a novel dietary risk factor, dietary glycemic index (dGI), and body mass index (BMI) affect the risk for age-related macular degeneration (AMD).
We used a case-control design with 962 subjects originally recruited through the Age-Related Eye Disease Study (AREDS) Genetic Repository. After excluding those with missing covariates or invalid calorie intake (n=23), diabetes (n=59), and non-Caucasian race (n=16), 864 participants were used in this study, including 209 AREDS category 1 participants (control group), 354 category 2 or 3 participants (drusen group), and 301 category 4 participants (advanced AMD group). A total of 25 single nucleotide polymorphisms (SNPs) selected from IGF-1 (n=9), IGF-2 (n=1), IGF binding protein 1 (IGFBP1) (n=3), IGFBP3 (n=3), acid-labile subunit of IGFBP (IGFALS) (n=2), IGF1 receptor (IGF1R) (n=4), and IGF2R (n=3) were genotyped. SNP-AMD associations were measured with genotype-, allele X2 tests and Armitage’s trend test. Odds ratios (OR), 95% confidence intervals (CIs) and SNP-exposure interactions were evaluated by multivariate logistic regression.
One SNP (rs2872060) in IGF1R revealed a significant association with advanced AMD (P-Allele=0.0009, P-Trend=0.0008; significance level was set at 0.05/25=0.002 for multiple comparisons). The risk allele (G) in the heterozygous and homozygous state (OR=1.67 and 2.93; 95% CI: 1.03-2.71 and 1.60-5.36, respectively) suggests susceptibility and suggests an additive effect on AMD risk. Further stratification analysis remained significant for both neovascularization (OR=1.49 and 2.61; 95% CI: 0.90-2.48 and 1.39-4.90, respectively) and geographic atrophy (OR=2.57 and 4.52; 95% CI: 0.99-6.71 and 1.49-13.74, respectively). The G allele interaction analysis with BMI was significant for neovascularization (P=0.042) but not for geographic atrophy (P=0.47). No significant interaction was found with dGI.
These data suggest a role of IGF1R on the risk for advanced AMD in this group of subjects.
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