Richardson Andrea J, Islam F M Amirul, Guymer Robyn H, Baird Paul N
Centre for Eye Research Australia, University of Melbourne, East Melbourne, Victoria, Australia.
Invest Ophthalmol Vis Sci. 2009 Feb;50(2):540-3. doi: 10.1167/iovs.08-2423. Epub 2008 Sep 20.
Several single-nucleotide polymorphisms (SNPs) in the C2 and BF genes have been associated with age-related macular degeneration (AMD) in Caucasian populations from the United States. The study was conducted to evaluate whether these SNPs are also associated with AMD in persons of Anglo-Celtic ethnicity in an Australian population.
Included in the study were 565 persons with AMD and 204 ethnically matched control subjects. All participants completed a standard health questionnaire, were given a fundus examination, and provided a blood sample for DNA extraction. Alleles were determined by a matrix-assisted desorption ionization-time of flight (MALDI-TOF)-based approach followed by statistical analysis.
The C2 and BF genes indicated significant association with AMD of only two SNPs; rs547154 (IVS10) in the C2 gene (P=9.1 x 10(-5)) and rs641153 (R32Q) in the BF gene (P=7.0 x 10(-5)). No association with AMD was found for SNP rs9332739 (E318D) in the C2 gene or for rs4151667 (L9H), rs1048709 (R150R), rs4151659 (K565E), or rs2072633 (IVS17) in the BF gene. A protective haplotype of variants IVS10 and R32Q was associated with AMD (OR 0.29, 95% CI 0.20-0.42).
In this study, the association of the IVS10 and R32Q variants in the C2 and BF genes in AMD was replicated. Haplotype analysis indicated association of these variants with AMD in an Australian population. Both IVS10 and R32Q variants were in strong linkage disequilibrium with each other (r(2)=0.96). Although the E318D and L9H variants have shown association with AMD in previous studies, the findings were not in agreement. This demonstrates a refined pattern of association of these rare variants with AMD.
在美国白种人群中，补体C2（C2）基因和B因子（BF）基因中的多个单核苷酸多态性（SNP）与年龄相关性黄斑变性（AMD）相关。本研究旨在评估这些SNP在澳大利亚盎格鲁 - 凯尔特族人群中是否也与AMD相关。
本研究纳入了565例AMD患者和204例种族匹配的对照受试者。所有参与者均完成了标准健康问卷，接受了眼底检查，并提供了用于DNA提取的血样。通过基于基质辅助激光解吸电离飞行时间（MALDI - TOF）的方法确定等位基因，随后进行统计分析。
C2和BF基因仅显示两个SNP与AMD有显著关联；C2基因中的rs547154（IVS10）（P = 9.1×10⁻⁵）和BF基因中的rs641153（R32Q）（P = 7.0×10⁻⁵）。未发现C2基因中的SNP rs9332739（E318D）或BF基因中的rs4151667（L9H）、rs104,8709（R150R）、rs4151659（K565E）或rs2072633（IVS17）与AMD相关。IVS10和R32Q变异的一种保护性单倍型与AMD相关（比值比0.29，95%可信区间0.20 - 0.42）。
在本研究中，C2和BF基因中的IVS10和R32Q变异与AMD的关联得到了重复验证。单倍型分析表明这些变异在澳大利亚人群中与AMD相关。IVS10和R32Q变异彼此处于强连锁不平衡状态（r² = 0.96）。尽管E318D和L9H变异在先前研究中显示与AMD相关，但本研究结果并不一致。这表明了这些罕见变异与AMD关联的精细模式。
