Moroldo M B, Donnelly P, Saunders J, Glass D N, Giannini E H
Children's Hospital Medical Center, University of Cincinnati College of Medicine, Ohio, USA.
Arthritis Rheum. 1998 Sep;41(9):1620-4. doi: 10.1002/1529-0131(199809)41:9<1620::AID-ART12>3.0.CO;2-L.
To determine if HLA class I and II alleles previously found to be associated with (or protective against) pauciarticular-onset juvenile rheumatoid arthritis (pauci-onset JRA) in population-association studies are transmitted from heterozygous parents to an extent different from the expected 50%.
One hundred one Caucasian North American families that had a child with pauci-onset JRA and at least 1 parent who was heterozygous for the allele of interest were available for analysis. Both biologic parents and all children (affected and unaffected) were typed for HLA class I and II alleles. The transmission disequilibrium test (TDT) was used to determine if affected offspring received the disease-associated (or protective) allele more (or less) frequently than its alternate allele. In families in which an unaffected sibling was available, the unmatched chi-square test was used to determine if a meiotic segregation distortion bias existed.
HLA class I alleles A2, B27, and B35 showed a significantly higher than expected frequency of transmission to affected offspring, as did class II alleles DR5 and DR8. HLA-DR4 was found to be transmitted significantly less frequently than expected to affected, but not unaffected, offspring. All alleles that showed an excess transmission to affected offspring were transmitted to unaffected offspring at expected rates. When the data were stratified by age and sex, the likelihood of transmission of some of the alleles was strongly influenced by these variables. For example, excess transmission of HLA-DR5 was found exclusively in female patients who were younger at the time of disease onset.
Results from these family-based studies rule out the possibility that HLA disease associations found in earlier studies were a result of population stratification and establish linkage and association between the major histocompatibility complex and pauci-onset JRA.
确定在人群关联研究中先前发现与少关节型幼年类风湿关节炎（少发型幼年类风湿关节炎）相关（或具有保护作用）的HLA I类和II类等位基因，从杂合子父母处的传递情况是否与预期的50%不同。
有101个北美白人家族可供分析，这些家族中有一个患少发型幼年类风湿关节炎的孩子，且至少有1名父母对感兴趣的等位基因是杂合的。对生物学父母和所有孩子（患病和未患病）进行HLA I类和II类等位基因分型。采用传递不平衡检验（TDT）来确定患病后代获得疾病相关（或保护性）等位基因的频率是否高于（或低于）其替代等位基因。在有未患病同胞的家族中，采用非配对卡方检验来确定是否存在减数分裂分离畸变偏差。
HLA I类等位基因A2、B27和B35向患病后代的传递频率显著高于预期，II类等位基因DR5和DR8也是如此。发现HLA - DR4向患病后代的传递频率显著低于预期，但向未患病后代的传递频率并非如此。所有向患病后代过度传递的等位基因向未患病后代的传递率均符合预期。当数据按年龄和性别分层时，某些等位基因的传递可能性受这些变量的强烈影响。例如，仅在疾病发作时年龄较小的女性患者中发现HLA - DR5的过度传递。
这些基于家族的研究结果排除了早期研究中发现的HLA疾病关联是人群分层结果的可能性，并确立了主要组织相容性复合体与少发型幼年类风湿关节炎之间的连锁和关联。
