Servicio de Inmunología, Instituto de Biomedicina, Hospital Universitario Virgen del Rocío, Avda Manuel Siurot s/n, 41013, Seville, Spain.
Hum Genet. 2010 Aug;128(2):221-9. doi: 10.1007/s00439-010-0844-1. Epub 2010 Jun 12.
Human HAVCR1 gene maps on 5q33.2, a region linked with susceptibility to allergic and autoimmune diseases. The aims of the present study were to define the haplotypes of HAVCR1 gene taking into account both HapMap Project SNP haplotypes and exon 4 variants, to investigate a possible relationship between these haplotypes and mRNA expression levels, and to assess whether HAVCR1 gene is involved in susceptibility to rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Genotyping of three ins/del variants in the exon 4 was performed by fragment length analysis. Five tag SNPs genotypes and mRNA levels were determined using TaqMan assays. We defined four major haplotypes in our population: the two major haplotypes (named haplotypes A and B) bear both the 5383_5397del variant and the two most common SNP sets found in the CEU population. Quantification analysis revealed that genotype B/B had the highest median of mRNA expression levels (vs. BX + XX, p < 0.0001). Additionally, frequency of the genotype BB was significantly higher in RA patients than in controls (12.3 vs. 5.9% in controls, p = 0.0046, p (c) = 0.014, OR = 2.23, 95% CI 1.23-4.10). Our results support a relationship between HAVCR1 haplotypes and mRNA expression levels, and suggest an association of this gene with autoimmune diseases.
人类 HAVCR1 基因位于 5q33.2，该区域与过敏和自身免疫性疾病的易感性相关。本研究的目的是定义 HAVCR1 基因的单倍型，同时考虑 HapMap 项目 SNP 单倍型和外显子 4 变异，研究这些单倍型与 mRNA 表达水平之间的可能关系，并评估 HAVCR1 基因是否与类风湿关节炎 (RA) 和系统性红斑狼疮 (SLE) 的易感性有关。通过片段长度分析对外显子 4 中的三个插入/缺失变体进行基因分型。使用 TaqMan 测定法确定五个标记 SNP 基因型和 mRNA 水平。我们在人群中定义了四个主要的单倍型：两个主要的单倍型（命名为单倍型 A 和 B）都携带 5383_5397del 变体和在 CEU 人群中发现的两个最常见的 SNP 集。定量分析显示，基因型 B/B 的 mRNA 表达水平中位数最高（与 BX + XX 相比，p<0.0001）。此外，RA 患者中基因型 BB 的频率明显高于对照组（12.3%对对照组的 5.9%，p=0.0046，p(c)=0.014，OR=2.23，95%CI 1.23-4.10）。我们的结果支持 HAVCR1 单倍型与 mRNA 表达水平之间的关系，并表明该基因与自身免疫性疾病有关。
