HTRA1基因中标签单核苷酸多态性rs3793917和rs11200638之间的基因间区域表明与年龄相关性黄斑变性有关联。
An intergenic region between the tagSNP rs3793917 and rs11200638 in the HTRA1 gene indicates association with age-related macular degeneration.
作者信息
Richardson Andrea J, Islam F M Amirul, Aung Khin Zaw, Guymer Robyn H, Baird Paul N
机构信息
Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.
出版信息
Invest Ophthalmol Vis Sci. 2010 Oct;51(10):4932-6. doi: 10.1167/iovs.09-5114. Epub 2010 May 5.
PURPOSE
There is still a debate as to whether the LOC387715 or HTRA1 genes represent the key significant association identified with age-related macular degeneration (AMD) on the long arm of chromosome 10, region 26.
METHODS
An Australian patient cohort was genotyped by using tagged single nucleotide polymorphisms (tSNPs) to identify a causal SNP within this region.
RESULTS
Multiple tSNPs across the region showed association with AMD with the tSNP rs3793917 (odds ratio [OR], 3.45; 95% confidence interval [CI], 2.36-5.05, P = 2.8 × 10(-13)) having the highest association with AMD. This tSNP occurred in the intergenic region between the LOC387715 and HTRA1 genes. A second tSNP rs2672587 (OR, 2.92; 95% CI, 2.04-4.17; P = 7.7 × 10(-11)) located in intron 1 of the HTRA1 gene had the second highest association with AMD. After logistic regression analysis, the only tSNP to survive covariate testing was rs3793917, which occurred in the same LD block as the HTRA1 promoter SNP rs11200638 (r(2) = 0.88, D' = 0.97).
CONCLUSIONS
The findings indicate that the intergenic region between the tSNP rs3793917 and the SNP rs11200638 in the HTRA1 gene is the most likely site explaining the significant association with AMD.
目的
关于LOC387715基因或HTRA1基因是否代表与10号染色体长臂26区年龄相关性黄斑变性（AMD）相关的关键显著关联，仍存在争议。
方法
利用标签单核苷酸多态性（tSNP）对一组澳大利亚患者进行基因分型，以确定该区域内的因果单核苷酸多态性。
结果
该区域的多个tSNP显示与AMD相关，其中tSNP rs3793917（优势比[OR]，3.45；95%置信区间[CI]，2.36 - 5.05，P = 2.8×10⁻¹³）与AMD的关联性最高。此tSNP位于LOC387715和HTRA1基因之间的基因间区域。位于HTRA1基因内含子1的第二个tSNP rs2672587（OR，2.92；95% CI，2.04 - 4.17；P = 7.7×10⁻¹¹）与AMD的关联性次之。经过逻辑回归分析，唯一在协变量检验中存活的tSNP是rs3793917，它与HTRA1启动子单核苷酸多态性rs11200638位于同一个连锁不平衡（LD）块中（r² = 0.88，D' = 0.97）。
结论
研究结果表明，tSNP rs3793917与HTRA1基因中的单核苷酸多态性rs11200638之间的基因间区域是最有可能解释与AMD显著关联的位点。
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