Department of Genetics, Dr. G. Venkataswamy Eye Research Institute, Aravind Medical Research Foundation, Aravind Eye Hospital, Madurai, Tamil Nadu, India.
PLoS One. 2012;7(3):e33001. doi: 10.1371/journal.pone.0033001. Epub 2012 Mar 8.
We investigated whether previously reported single nucleotide polymorphisms (SNPs) of EPHA2 in European studies are associated with cataract in India.
We carried out a population-based genetic association study. We enumerated randomly sampled villages in two areas of north and south India to identify people aged 40 and over. Participants attended a clinical examination including lens photography and provided a blood sample for genotyping. Lens images were graded by the Lens Opacification Classification System (LOCS III). Cataract was defined as a LOCS III grade of nuclear ≥4, cortical ≥3, posterior sub-capsular (PSC) ≥2, or dense opacities or aphakia/pseudophakia in either eye. We genotyped SNPs rs3754334, rs7543472 and rs11260867 on genomic DNA extracted from peripheral blood leukocytes using TaqMan assays in an ABI 7900 real-time PCR. We used logistic regression with robust standard errors to examine the association between cataract and the EPHA2 SNPs, adjusting for age, sex and location.
7418 participants had data on at least one of the SNPs investigated. Genotype frequencies of controls were in Hardy-Weinberg Equilibrium (p>0.05). There was no association of rs3754334 with cataract or type of cataract. Minor allele homozygous genotypes of rs7543472 and rs11260867 compared to the major homozygote genotype were associated with cortical cataract, Odds ratio (OR) = 1.8, 95% Confidence Interval (CI) (1.1, 3.1) p = 0.03 and 2.9 (1.2, 7.1) p = 0.01 respectively, and with PSC cataract, OR = 1.5 (1.1, 2.2) p = 0.02 and 1.8 (0.9, 3.6) p = 0.07 respectively. There was no consistent association of SNPs with nuclear cataract or a combined variable of any type of cataract including operated cataract.
Our results in the Indian population agree with previous studies of the association of EPHA2 variants with cortical cataracts. We report new findings for the association with PSC which is particularly prevalent in Indians.
我们调查了欧洲研究中先前报道的 EphA2 单核苷酸多态性（SNP）是否与印度的白内障有关。
我们进行了一项基于人群的遗传关联研究。我们在印度北部和南部两个地区随机抽取了一些村庄进行计数，以确定年龄在 40 岁及以上的人群。参与者参加了临床检查，包括晶状体摄影，并提供了血液样本进行基因分型。晶状体图像通过晶状体混浊分类系统（LOCS III）进行分级。白内障定义为双眼核混浊程度≥4、皮质混浊程度≥3、后囊下混浊程度≥2、或致密混浊或无晶状体/假晶状体。我们使用 TaqMan 测定法在 ABI 7900 实时 PCR 中对从外周血白细胞中提取的基因组 DNA 上的 rs3754334、rs7543472 和 rs11260867 SNP 进行基因分型。我们使用具有稳健标准误差的逻辑回归来检验白内障与 EphA2 SNP 之间的关联，调整年龄、性别和位置。
7418 名参与者至少有一项调查 SNP 的数据。对照组的基因型频率符合 Hardy-Weinberg 平衡（p>0.05）。rs3754334 与白内障或白内障类型无关。与主要纯合基因型相比，rs7543472 和 rs11260867 的次要等位基因纯合基因型与皮质白内障相关，优势比（OR）分别为 1.8（95%置信区间（CI）（1.1，3.1），p=0.03）和 2.9（1.2，7.1），p=0.01），与 PSC 白内障相关，OR 分别为 1.5（1.1，2.2），p=0.02 和 1.8（0.9，3.6），p=0.07。SNP 与核性白内障或包括手术性白内障在内的任何类型白内障的综合变量之间没有一致的关联。
我们在印度人群中的结果与 EphA2 变异与皮质白内障相关的先前研究一致。我们报告了与 PSC 相关的新发现，PSC 在印度人中尤为普遍。
