Complement factor H variant Y402H is a major risk determinant for geographic atrophy and choroidal neovascularization in smokers and nonsmokers
Complement factor H variant Y402H is a major risk determinant for geographic atrophy and choroidal neovascularization in smokers and nonsmokers
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DOI：
10.1167/iovs.05-1143
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发表时间：
2006-02-01
影响因子：
4.4
通讯作者：
Yates, JRW
中科院分区：
文献类型：
--
作者：
Sepp, T;Khan, JC;Yates, JRW
目的。补体因子H(CFH)基因Y402H(1277T->；C)多态性与老年性黄斑变性(AMD)的易感性有关。这项研究的目的是在英国人群中证实这种关联，确定这种关联是否同时存在于地理萎缩(GA)和脉络膜新生血管(CNV)，并调查与吸烟的相互作用。方法：对443例AMD患者和262名配偶进行病例对照研究。所有受试者均完成健康和生活方式问卷调查，进行眼底照相眼科检查，并进行基因分型。结果病例组C等位基因频率和CC基因型频率均显著高于对照组。与TT型相比，CT型和CC型与AMD发病的优势比分别为3.1(CI 2.0~4.6)和6.3(CI 3.8~10.4)。在仅限于GA或CNV病例的亚组分析中，结果相似。对从未吸烟、中度吸烟者或重度吸烟者(吸烟年限为20年)的亚组分析也有类似的发现。CC基因的吸烟量较大的人可能特别危险。在有和没有AMD家族史的病例中，CC基因型的频率没有显著差异。没有证据表明基因型对发病年龄有任何影响。结论：在英国人群中，CFH Y402H变异与GA和CNV密切相关。在吸烟者和不吸烟者中，这种联系是相似的。CC基因的重度吸烟者可能是特别危险的。
PURPOSE. The complement factor H (CFH) gene polymorphism Y402H ( 1277T -> C) has been associated with susceptibility to age-related macular degeneration (AMD). The purpose of this study was to confirm this association in a U. K. population, to determine whether the association holds for both geographic atrophy (GA) and choroidal neovascularization (CNV), and to investigate interactions with smoking.METHODS. A case-control study was undertaken in 443 cases of AMD, with 262 spouses as control subjects. All subjects completed a health and lifestyle questionnaire, had an ophthalmic assessment with fundus photography, and were genotyped.RESULTS. The frequencies of the C allele and CC genotype were significantly higher in cases than in controls. In comparison to the TT genotype, the odds ratios for AMD associated with the CT and CC genotypes were 3.1 (CI 2.0-4.6) and 6.3 ( CI 3.8-10.4), respectively. The results were similar in subgroup analyses confined to cases with GA or CNV. The findings were also similar for subgroup analyses restricted to subjects who had never smoked, moderate smokers, or heavier smokers (> 20 pack years of smoking). Heavier smokers with the CC genotype may be particularly at risk. The frequency of the CC genotype did not differ significantly between cases with and without a family history of AMD. There was no evidence that genotype had any influence on age at onset of disease.CONCLUSIONS. The CFH Y402H variant is strongly associated with both GA and CNV in the U. K. population. This association is similar in smokers and nonsmokers. Heavier smokers with the CC genotype may be at particular risk.