韩国圆锥角膜患者白细胞介素1β（IL1B）启动子中-31T>C和-511 C>T多态性的关联
Association of -31T>C and -511 C>T polymorphisms in the interleukin 1 beta (IL1B) promoter in Korean keratoconus patients.
作者信息
Kim So-Hee, Mok Jee-Won, Kim Hyun-Seok, Joo C K
机构信息
Department of Life Science, Catholic University of Korea, Seoul, Korea.
出版信息
Mol Vis. 2008;14:2109-16. Epub 2008 Nov 21.
PURPOSE
To investigate the genetic association between unrelated Korean keratoconus patients and interleukin 1 alpha (IL1A), interleukin 1 beta (IL1B), and IL1 receptor antagonist (IL1RN) gene polymorphisms.
METHODS
We investigated the association between IL1A (rs1800587, rs2071376, and rs17561), IL1B (rs1143627, rs16944, rs1143634, and rs1143633), and IL1RN (rs419598, rs423904, rs424078, and rs315952, variable number tandem repeat [VNTR]) polymorphisms in 100 unrelated Korean keratoconus patients. One hundred control individuals without any corneal disease were selected from the general population. Polymerase chain reaction (PCR) - restriction fragment length polymorphism (RFLP) analysis and direct sequencing were used to screen for genetic variations in the IL1 gene cluster. Haplotypes for the IL1 gene cluster were constructed using Haploview version 4.0.
RESULTS
We analyzed a total of 12 polymorphic sites in the IL1 gene cluster. Among them, the -511 (rs16944) and -31 (rs1143627) positions in the promoter region of IL1B were significantly different between patient and control groups. The C allele of rs16944 (-511C>T, p=0.022, odds ratio of risk [OR]=1.46, 95% confidence intervals [CI] 0.94<2.27) and the T allele of rs1143627 (-31T>C, p=0.025, OR=1.43, 95% CI 0.92<2.22) were associated with a significantly increased risk of keratoconus in Korean patients. Linkage of the two alleles, -31C and -511T, was associated with an increased risk for keratoconus with OR=2.38 (p=0.012, 95% CI=1.116-5.046). The *C/*A genotype of rs2071376 in IL1A intron 6 was significantly different between the keratoconus patients and control subjects (p=0.034, OR=0.59, 95% CI 0.32<1.11). Other polymorphisms did not show an association with keratoconus risk.
CONCLUSIONS
This is the first report of IL1 gene cluster mutation screening in Korean keratoconus patients. Significant differences in allelic frequency of IL1B between keratoconus patients and the control group suggest that IL1B polymorphisms may play a role in the susceptibility of unrelated Koreans to develop keratoconus.
目的
研究无关的韩国圆锥角膜患者与白细胞介素1α（IL1A）、白细胞介素1β（IL1B）及IL1受体拮抗剂（IL1RN）基因多态性之间的遗传关联。
方法
我们调查了100例无关的韩国圆锥角膜患者中IL1A（rs1800587、rs2071376和rs17561）、IL1B（rs1143627、rs16944、rs1143634和rs1143633）以及IL1RN（rs419598、rs423904、rs424078和rs315952，可变数目串联重复序列[VNTR]）多态性。从普通人群中选取100名无任何角膜疾病的对照个体。采用聚合酶链反应（PCR）-限制性片段长度多态性（RFLP）分析和直接测序来筛查IL1基因簇中的遗传变异。使用Haploview 4.0版本构建IL1基因簇的单倍型。
结果
我们共分析了IL1基因簇中的12个多态性位点。其中，IL1B启动子区域的-511（rs16944）和-31（rs1143627）位点在患者组和对照组之间存在显著差异。rs16944的C等位基因（-511C>T，p=0.022，风险比[OR]=1.46，95%置信区间[CI] 0.94<2.27）和rs1143627的T等位基因（-31T>C，p=0.025，OR=1.43，95% CI 0.92<2.22）与韩国患者圆锥角膜风险显著增加相关。两个等位基因-31C和-511T的连锁与圆锥角膜风险增加相关，OR=2.38（p=0.012，95% CI=1.116 - 5.046）。IL1A内含子6中rs2071376的*C/*A基因型在圆锥角膜患者和对照受试者之间存在显著差异（p=0.034，OR=0.59，95% CI 0.32<1.11）。其他多态性与圆锥角膜风险无关联。
结论
这是关于韩国圆锥角膜患者IL1基因簇突变筛查的首份报告。圆锥角膜患者和对照组之间IL1B等位基因频率的显著差异表明，IL1B多态性可能在无关的韩国人患圆锥角膜的易感性中起作用。
Zotero 插件