A functional haplotype of the PADI4 gene associated with rheumatoid arthritis in a Japanese population is not associated in a United Kingdom population
A functional haplotype of the PADI4 gene associated with rheumatoid arthritis in a Japanese population is not associated in a United Kingdom population
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DOI：
10.1002/art.20169
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发表时间：
2004-04-01
影响因子：
--
通讯作者：
Worthington, J
中科院分区：
文献类型：
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作者：
Barton, A;Bowes, J;Worthington, J
目标。在后基因组研究时代，基于连锁和关联的策略开始揭示新的复杂疾病基因。采用这种方法，最近在日本人群中发现了一种功能单倍型的PADI4基因(PADI4)，该基因与类风湿性关节炎(RA)易感。在本研究中，我们调查了PADI4基因的单核苷酸多态(SNPs)与英国人群中类风湿性关节炎的关联。研究了4个外显子SNP(PADI4_*G/A、PADI4_90*T/C、PADI4_92*G/C和PADI4_104*T/C)与PADI4基因的关联。采用5‘端等位基因辨别法进行基因分型。使用期望最大化算法生成估计的单倍型，并比较839例英国无关高加索类风湿性关节炎患者和481例正常对照人群的SNPs和单倍型频率。在英国人群中，这4个SNPs的等位基因频率与日本对照人群中报道的相似，但没有一个与RA相关。与日本人群一样，英国人群中的SNPs决定了两种主要的单倍型，但均与类风湿性关节炎无关(P=0.79)。日本人群中与RA相关的PADI4易感性单倍型与英国人群中的RA无关。参与瓜氨酸化途径的其他基因仍然是RA的重要候选基因，需要进一步研究。
Objective. In the era of postgenomic research, linkage- and association-based strategies are beginning to reveal novel complex disease genes. Using such an approach, a functional haplotype of the peptidylarginine deiminase 4 gene (PADI4) has recently been identified as a gene conferring susceptibility to rheumatoid arthritis (RA) in a Japanese population. In the present study, we investigated the association of single-nucleotide polymorphisms (SNPs) in the PADI4 gene with RA in a UK population.Methods. Association with 4 exonic SNPs (padi4_89*G/A, padi4_90*T/C, padi4_92*G/C, and padi4_104*T/C), mapping to the PADI4 gene and defining a haplotype previously reported to be associated with RA, was investigated. Genotyping was performed using 5' allelic discrimination assays. Estimated haplotypes were generated using the expectation-maximization algorithm, and frequencies of the SNPs and haplotypes were compared between unrelated Caucasian RA patients from the UK (n = 839) and population controls (n = 481).Results. Allele frequencies for the 4 SNPs in the UK population were similar to those reported in the Japanese control population, but none of these was associated with RA. As in the Japanese population, the SNPs in the UK population defined 2 major haplotypes, but neither was associated with RA (P = 0.79).Conclusion. A PADI4 susceptibility haplotype associated with RA in a Japanese population is not associated with RA in a UK population. Other genes involved in the citrullinating pathway remain strong candidate RA-susceptibility genes and require further investigation.