Analysis of Maternal-Offspring HLA Compatibility, Parent-of-Origin Effects, and Noninherited Maternal Antigen Effects for HLA-DRB1 in Systemic Lupus Erythematosus
Analysis of Maternal-Offspring HLA Compatibility, Parent-of-Origin Effects, and Noninherited Maternal Antigen Effects for HLA-DRB1 in Systemic Lupus Erythematosus
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DOI：
10.1002/art.27426
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发表时间：
2010-06-01
影响因子：
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通讯作者：
Barcellos, Lisa F.
中科院分区：
文献类型：
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作者：
Bronson, Paola G.;Komorowski, Leanne K.;Barcellos, Lisa F.
Objective.系统性红斑狼疮（SLE）的遗传易感性已得到充分证实，其中HLA II类DRB 1和DQB 1基因座表现出最强的关联。然而，除了危险等位基因的遗传传递之外，HLA还可能通过新的生物学机制影响SLE。已有证据表明，SLE中母亲-子女HLA II类相容性增加，其他自身免疫性疾病中母亲与父亲的传播率（起源父母效应）和非传播率（非遗传性母体抗原[NIMA]效应）存在差异。因此，我们研究了SLE患者的母-子HLA相容性、父母来源效应和DRB 1的NIMA效应。该队列包括707个SLE家族和188对独立的健康母子（共2，497人）。进行了以家庭为基础的关联检验，以比较传播与非传播的等位基因（传播不平衡检验）以及母亲与父亲传播（起源父母）和非传播的等位基因（使用卡方异质性检验）。根据后代的性别对分析进行分层。SLE家系中受母系影响的后代DRB 1相容性与受父系影响的后代相容性和独立对照的母子对进行比较（使用Fisher检验），并仅限于SLE的男性和未孕女性后代。正如预期的那样，DRB 1与SLE相关（P < 1 × 10 - 4）。然而，SLE患儿的母亲与父亲相比，DRB 1等位基因的传播和非传播频率相似，包括已知的SLE风险等位基因HLA-DRB 1 *0301、*1501和 *0801。结论母儿相容性与SLE无相关性。母-子HLA相容性、双亲起源效应和DRB 1的NIMA效应不太可能在SLE中发挥作用。
Objective. Genetic susceptibility to systemic lupus erythematosus (SLE) is well established, with the HLA class II DRB1 and DQB1 loci demonstrating the strongest association. However, HLA may also influence SLE through novel biologic mechanisms in addition to genetic transmission of risk alleles. Evidence for increased maternal-offspring HLA class II compatibility in SLE and differences in maternal versus paternal transmission rates (parent-of-origin effects) and nontransmission rates (noninherited maternal antigen [NIMA] effects) in other autoimmune diseases have been reported. Thus, we investigated maternal-offspring HLA compatibility, parent-of-origin effects, and NIMA effects at DRB1 in SLE.Methods. The cohort comprised 707 SLE families and 188 independent healthy maternal-offspring pairs (total of 2,497 individuals). Family-based association tests were conducted to compare transmitted versus nontransmitted alleles (transmission disequilibrium test) and both maternally versus paternally transmitted (parent-of-origin) and nontransmitted alleles (using the chi-square test of heterogeneity). Analyses were stratified according to the sex of the offspring. Maternally affected offspring DRB1 compatibility in SLE families was compared with paternally affected offspring compatibility and with independent control maternal-offspring pairs (using Fisher's test) and was restricted to male and nulligravid female offspring with SLE.Results. As expected, DRB1 was associated with SLE (P < 1 x 10(-4)). However, mothers of children with SLE had similar transmission and nontransmission frequencies for DRB1 alleles when compared with fathers, including those for the known SLE risk alleles HLA-DRB1*0301, *1501, and *0801. No association between maternal-offspring compatibility and SLE was observed.Conclusion. Maternal-offspring HLA compatibility, parent-of-origin effects, and NIMA effects at DRB1 are unlikely to play a role in SLE.