Associations between Genetic Polymorphisms of Insulin-like Growth Factor Axis Genes and Risk for Age-Related Macular Degeneration
Associations between Genetic Polymorphisms of Insulin-like Growth Factor Axis Genes and Risk for Age-Related Macular Degeneration
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DOI：
10.1167/iovs.11-7782
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发表时间：
2011-11-01
影响因子：
4.4
通讯作者：
Taylor, Allen
中科院分区：
文献类型：
--
作者：
Chiu, Chung-Jung;Conley, Yvette P.;Taylor, Allen
目的.探讨胰岛素样生长因子（IGF）轴基因与新的饮食风险因子--饮食血糖指数（dGI）和体重指数（BMI）是否影响年龄相关性黄斑变性（AMD）的风险。这项病例对照研究涉及962名受试者，最初是通过眼相关眼病研究（AREDS）基因库招募的。在排除那些缺失协变量或无效卡路里摄入量（n = 23），糖尿病（n = 59）和非高加索人种（n = 16）后，使用了864名参与者，包括209名AREDS 1类参与者（对照组），354名2类或3类参与者（玻璃疣组）和301名4类参与者（晚期AMD组）。共25个单核苷酸多态性（SNP），选自IGF-1（n = 9）、IGF-2（n = 1）、IGF结合蛋白1（IGFBP 1; n = 3）、IGFBP 3（n = 3）、IGFBP酸不稳定亚基（IGFALS; n = 2）、IGF 1受体（IGF 1 R; n = 4）和IGF 2 R（n = 3）。SNP-AMD的关联性用基因型、等位基因卡方检验和Armitage趋势检验来测量。通过多变量logistic回归分析评估比值比（OR）、95%置信区间（CI）和SNP-暴露交互作用。IGF 1 R中的一个SNP（rs 2872060）显示与晚期AMD显著相关（P等位基因= 0.0009，P趋势= 0.0008;多重比较的显著性水平设定为0.05/25 = 0.002）。杂合子和纯合子状态下的风险等位基因（G）（OR分别为1.67和2.93; 95%CI分别为1.03-2.71和1.60-5.36）表明AMD风险的易感性和累加效应。进一步的分层分析对新生血管形成（OR，1.49和2.61; 95% CI，分别为0.90-2.48和1.39-4.90）和地图样萎缩（OR，2.57和4.52; 95% CI，分别为0.99-6.71和1.49-13.74）仍具有显著性。G等位基因与BMI的相互作用分析对新生血管形成有显著意义（P = 0.042），但对地图样萎缩无显著意义（P = 0.47）。未发现与dGI的显著相互作用。这些数据表明IGF 1 R在这组受试者中对晚期AMD风险的作用。（Invest Ophthalmol维斯科学。2011;52：9099-9107）DOI：10.1167/iovs.11-7782
PURPOSE. To investigate whether insulin-like growth factor (IGF) axis genes, together with a novel dietary risk factor, the dietary glycemic index (dGI), and body mass index (BMI) affect the risk for age-related macular degeneration (AMD).METHODS. This case-control study involved 962 subjects originally recruited through the Age-Related Eye Disease Study (AREDS) Genetic Repository. After those with missing covariates or invalid calorie intake (n = 23), diabetes (n = 59), and non-Caucasian race (n = 16) were excluded, 864 participants were used, 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 geno-type, allele chi(2) tests and Armitage's trend test. Odds ratios (OR), 95% confidence intervals (CIs), and SNP-exposure interactions were evaluated by multivariate logistic regression.RESULTS. One SNP (rs2872060) in IGF1R revealed a significant association with advanced AMD (P-allele = 0.0009, P-trend = 0.0008; the significance level was set at 0.05/25 = 0.002 for multiple comparisons). The risk allele (G) in the heterozygous and homozygous states (OR, 1.67 and 2.93; 95% CI, 1.03-2.71 and 1.60-5.36, respectively) suggests susceptibility and 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.CONCLUSIONS. These data suggest a role of IGF1R on the risk for advanced AMD in this group of subjects. (Invest Ophthalmol Vis Sci. 2011;52:9099-9107) DOI: 10.1167/iovs.11-7782