Barnetche T, Constantin A, Gourraud P-A, Abbal M, Garnier J-G, Cantagrel A, Cambon-Thomsen A
Institut National de la Santé et de la Recherché Médicale, Unit 558, Department of Public Health and Epidemiology, Faculty of Medicine Purpan, University Paul Sabatier Toulouse III, F-31073 Toulouse, France.
Tissue Antigens. 2006 Nov;68(5):390-8. doi: 10.1111/j.1399-0039.2006.00693.x.
Within the major histocompatibility complex (MHC), the human leucocyte antigen (HLA)-DRB1 locus is clearly associated with rheumatoid arthritis (RA). Using a microsatellite (MSat) typing approach, we aimed to identify other loci associated with RA susceptibility and/or severity within the MHC. A panel of nine MSat HLA loci [D6S291, D6S2876 (G51152), D6S1666 (DQCAR II), D6S273, D6S2789 (TNFd), D6S2810 (MIB), D6S265, D6S2222, D6S2239], and HLA-A, -B and -DRB1 genes were typed in 170 RA cases and 282 controls. For susceptibility analysis, MSat and HLA allele distribution were compared between cases and controls, before and after stratification on HLA-DRB104. Haplotype frequencies were estimated using an expectation-maximization algorithm in a permutation test procedure. For severity analysis, we compared the distribution of structural damage score at onset and after 4 years of follow-up in RA cases carrying susceptibility alleles. Two MSat polymorphisms were positively associated with RA susceptibility: allele136 of D6S265 [odds ratio, OR (confidence interval, CI) = 1.55 (1.11-2.17), P= 0.007], allele116 of D6S2239 [OR = 1.34 (1-1.79), P= 0.03] and HLA-A2 [OR = 1.46 (1.08-1.98), P= 0.01]. Two MSat polymorphisms were negatively associated with RA susceptibility: allele133 of D6S273 [OR = 0.3 (0.1-0.75), P= 0.005] and allele177 of D6S291 [OR = 0.72 (0.53-0.96), P= 0.02]. The association between allele136 of D6S265 and RA susceptibility remained unchanged after stratification on HLA-DRB104. The haplotypic analysis showed an overrepresentation of D6S265136/HLA-A*02 haplotype, which suggests an effect independent of HLA-DRB1 locus in RA susceptibility. While HLA-A2 and HLA-DR4 were associated with RA severity, no MSat polymorphism was associated with structural damage score.
在主要组织相容性复合体（MHC）中，人类白细胞抗原（HLA）-DRB1基因座与类风湿关节炎（RA）明显相关。我们采用微卫星（MSat）分型方法，旨在确定MHC内与RA易感性和/或严重程度相关的其他基因座。在170例RA患者和282例对照中对一组9个MSat HLA基因座[D6S291、D6S2876（G51152）、D6S1666（DQCAR II）、D6S273、D6S2789（TNFd）、D6S2810（MIB）、D6S265、D6S2222、D6S2239]以及HLA-A、-B和-DRB1基因进行分型。对于易感性分析，在按HLA-DRB104分层前后，比较病例组和对照组之间的MSat和HLA等位基因分布。在排列检验程序中使用期望最大化算法估计单倍型频率。对于严重程度分析，我们比较了携带易感等位基因的RA患者发病时和随访4年后结构损伤评分的分布情况。两个MSat多态性与RA易感性呈正相关：D6S265的136等位基因[优势比，OR（置信区间，CI）=1.55（1.11 - 2.17），P = 0.007]、D6S2239 的116等位基因[OR = 1.34（1 - 1.79），P = 0.03]以及HLA-A2[OR = 1.46（1.08 - 1.98），P = 0.01]。两个MSat多态性与RA易感性呈负相关：D6S273的133等位基因[OR = 0.3（0.1 - 0.75），P = 0.005]和D6S291的177等位基因[OR = 0.72（0.53 - 0.96），P = 0.02]。在按HLA-DRB104分层后，D6S265的136等位基因与RA易感性之间的关联保持不变。单倍型分析显示D6S265136/HLA-A*02单倍型过度存在，这表明在RA易感性中存在独立于HLA-DRB1基因座的效应。虽然HLA-A2和HLA-DR4与RA严重程度相关，但没有MSat多态性与结构损伤评分相关。
