Age-Related Macular Degeneration Is Associated with the HLA-Cw*0701 Genotype and the Natural Killer Cell Receptor AA Haplotype
Age-Related Macular Degeneration Is Associated with the HLA-Cw*0701 Genotype and the Natural Killer Cell Receptor AA Haplotype
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DOI：
10.1167/iovs.08-1837
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发表时间：
2008-11-01
影响因子：
4.4
通讯作者：
Lotery, Andrew J.
中科院分区：
文献类型：
--
作者：
Goverdhan, Srinivas V.;Khakoo, Salim I.;Lotery, Andrew J.
目的。确定人类白细胞抗原 (HLA) C 及其同源杀伤细胞免疫球蛋白样受体 (KIR) 配体与年龄相关性黄斑变性 (AMD) 的关联。方法。使用 PCR-SSP（序列特异性引物）方法对 104 名 AMD 病例和 93 名对照者的 HLA I 类等位基因组（包括 HLA-C 主要等位基因）进行了基因分型。然后通过 PCR-SSP 对这个队列的 16 个 KIR 基因进行基因分型。然后比较 AMD 患者和正常对照受试者之间测试的 HLA/KIR 等位基因的频率。测试了 HLA-C1、-Cw* 07 和 -Cw* 0701 基因型及其与 KIR 基因型/单倍型的组合与 AMD 的关联。通过双尾 chi(2) 检验和应用于多重检验 (P-c) 的 Bonferroni 校正获得概率。 结果。经过 Logistic 回归分析，HLA-Cw* 0701 等位基因与抑制性 KIR AA 单倍型相结合与 AMD 相关（P = 0.006，P-c = 0.036，OR = 4.35，95% CI = 1.41-13.44）。结论。 HLA-Cw* 0701 等位基因和 KIR 单倍型 AA 与 AMD 相关。这种基因型组合表明自然杀伤细胞在 AMD 的发病机制中发挥作用。需要进行复制研究来证实这些新的 HLA-KIR 与 AMD 的关联。 （投资眼科可见科学。2008 年；49：5077-5082）DOI：10.1167/iovs.08-1837
PURPOSE. To determine the association of human leukocyte antigen (HLA) C and its cognate killer cell immunoglobulin-like receptor (KIR) ligands with age-related macular degeneration (AMD).METHODS. HLA class I allele groups including the HLA-C principal alleles were genotyped in a cohort of 104 AMD cases and 93 controls by using the PCR-SSP (sequence-specific primers) method. This cohort was then genotyped for 16 KIR genes by PCR-SSP. Frequencies of the tested HLA/ KIR alleles were then compared between patients with AMD and normal control subjects. HLA-C1, -Cw* 07, and -Cw* 0701 genotypes and their combinations with KIR genotypes/ haplotypes were tested for association with AMD. Probabilities were obtained with a two-tailed chi(2) test and Bonferroni correction applied for multiple testing (P-c).RESULTS. The HLA-Cw* 0701 allele, in combination with the inhibitory KIR AA haplotype was associated with AMD after logistic regression analysis (P = 0.006, P-c = 0.036, OR = 4.35, 95% CI = 1.41-13.44).CONCLUSIONS. The HLA-Cw* 0701 allele and KIR haplotype AA are associated with AMD. This genotype combination suggests that natural killer cells have a role in the pathogenesis of AMD. Replication studies are needed to confirm these novel HLA-KIR associations with AMD. (Invest Ophthalmol Vis Sci. 2008; 49: 5077-5082) DOI: 10.1167/iovs.08-1837