在印度患者中，10q26基因簇（LOC387715和HTRA1）中的变异与CFH一起，显示出年龄相关性黄斑变性风险增加。
Variants in the 10q26 gene cluster (LOC387715 and HTRA1) exhibit enhanced risk of age-related macular degeneration along with CFH in Indian patients.
作者信息
Kaur Inderjeet, Katta Saritha, Hussain Avid, Hussain Nazimul, Mathai Annie, Narayanan Raja, Hussain Anjli, Reddy Rajeev K, Majji Ajit B, Das Taraprasad, Chakrabarti Subhabrata
机构信息
Kallam Anji Reddy Molecular Genetics Laboratory, L.V. Prasad Eye Institute, Road No. 2, Banjara Hills, Hyderabad, India.
出版信息
Invest Ophthalmol Vis Sci. 2008 May;49(5):1771-6. doi: 10.1167/iovs.07-0560.
PURPOSE
Single nucleotide polymorphisms (SNPs) in the LOC387715 (rs10490924), HTRA1 (rs11200638), and CFH (rs1061170) genes have been implicated in age-related macular degeneration (AMD). The present study was undertaken to determine the involvement of the LOC387715 and HTRA1 in an AMD cohort from India.
METHODS
The coding region of LOC387715 (exon 1) and the promoter of HTRA1 were screened by resequencing in AMD cases and normal controls. Odds ratios were calculated to assess the risk of individual genotypes. Linkage disequilibrium (LD) and haplotype frequencies were estimated with Haploview software. Population attributable risk (PAR %) for the associated SNPs and their combined effects were calculated.
RESULTS
Resequencing revealed seven different SNPs in these genes, of which significant associations were noted with the risk alleles of rs10490924 (T allele; P = 5.34 x 10(-12)) in LOC387715, and rs11200638 (A allele; P = 4.32 x 10(-12)) and rs2672598 (C allele; P = 3.39 x 10(-11)) in HTRA1 among the cases. Correspondingly, the homozygous risk genotypes TT, AA, and CC in these SNPs exhibited higher disease odds and PAR %. rs10490924 and rs11200638 were in tight LD (D', 0.90; 95% CI, 0.84-0.93). G-C-T-A-C was the risk haplotype (P = 8.04 x 10(-15)), whereas the G-C-G-G-T haplotype was protective (P = 2.01 x 10(-4)). The combined effect of the CFH (CC) and LOC387715 (TT) risk genotypes exhibited a PAR of 93.7% (OR, 73.89; 95% CI, 8.69-628.13).
CONCLUSIONS
The present data provided an independent validation of the association of LOC387715 and HTRA1 SNPs, along with their risk estimates among Indian patients with AMD. These associations underscore their significant involvement in AMD susceptibility, which may be useful for predictive testing.
目的
LOC387715（rs10490924）、HTRA1（rs11200638）和CFH（rs1061170）基因中的单核苷酸多态性（SNP）与年龄相关性黄斑变性（AMD）有关。本研究旨在确定LOC387715和HTRA1在一组印度AMD患者中的作用。
方法
对AMD患者和正常对照进行重测序，以筛查LOC387715的编码区（外显子1）和HTRA1的启动子。计算优势比以评估个体基因型的风险。使用Haploview软件估计连锁不平衡（LD）和单倍型频率。计算相关SNP的人群归因风险（PAR%）及其联合效应。
结果
重测序揭示了这些基因中的7种不同SNP，其中rs10490924（T等位基因；P = 5.34×10⁻¹²）在LOC387715中的风险等位基因，以及rs11200638（A等位基因；P = 4.32×10⁻¹²）和rs2672598（C等位基因；P = 3.39×10⁻¹¹）在HTRA1中的风险等位基因与病例显著相关。相应地，这些SNP中的纯合风险基因型TT、AA和CC表现出更高的疾病优势比和PAR%。rs10490924和rs11200638处于紧密连锁不平衡（D'，0.90；95%CI，0.84 - 0.93）。G - C - T - A - C是风险单倍型（P = 8.04×10⁻¹⁵），而G - C - G - G - T单倍型具有保护作用（P = 2.01×10⁻⁴）。CFH（CC）和LOC387715（TT）风险基因型的联合效应显示PAR为93.7%（OR，73.89；95%CI，8.69 - 628.13）。
结论
本数据为LOC387715和HTRA1 SNP的关联及其在印度AMD患者中的风险估计提供了独立验证。这些关联强调了它们在AMD易感性中的重要作用，这可能有助于预测性检测。
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