Hizawa N, Collins G, Rafnar T, Huang S K, Duffy D L, Weber J L, Freidhoff L R, Ehrlich E, Marsh D G, Beaty T H, Barnes K C
Division of Clinical Immunology, The Johns Hopkins Asthma & Allergy Center, Baltimore, MD 21224, USA.
J Allergy Clin Immunol. 1998 Sep;102(3):443-8. doi: 10.1016/s0091-6749(98)70133-2.
Recently, we have obtained evidence for linkage between Der p 1-specific IgE antibodies and markers on chromosome 6p21 (HLA-D region) in a genome-wide screening in Caucasian families recruited as a part of the Collaborative Study on the Genetics of Asthma (CSGA).
Specific IgE antibodies toward different Dermatophagoides pteronyssinus (Der p) polypeptides were detected by immunoblotting analysis, and the transmission/disequilibrium test (TDT) was performed between specific IgE responsiveness toward each different Der p polypeptide and markers on chromosome 6p21 to better clarify the genetic contribution of HLA-D genes.
We studied 299 individuals in 45 Caucasian families participating in the CSGA. Serum samples from 137 individuals that showed elevated specific IgE antibodies toward the Der p crude allergen (> -0.5 log IU/mL) by ACCESS immunoassay were subjected to immunoblotting analysis. TDT was conducted between the presence of specific IgE antibodies toward each of 12 different Der p polypeptides and 4 polymorphic markers on chromosome 6p21.
The 196-bp allele of D6S1281 and the 104-bp allele of DQCAR showed significant excess transmission to specific IgE responders toward a particular Der p polypeptide (120 kd, 55 kd, 45 kd, or 37 kd). In contrast, the 200-bp allele of D6S1281 and the 204-bp allele of D6S291 showed significantly decreased transmission to specific IgE responders toward a particular Der p polypeptide (120 kd, 90 kd, 52 kd, or 45 kd). Deviation from the expected 50% transmission in heterozygous parents was statistically significant after correcting for multiple comparisons.
This study supported our previous findings that genes on chromosome 6p21 (HLA-D region) may influence the expression of Der p-specific IgE responsiveness in this Caucasian population. Our results, however, reveal the complexity of genetic regulations of Der p-specific IgE responsiveness by HLA-D genes, suggesting the strong influence of non-HLA loci and perhaps environmental factors for the development of Der p-specific IgE responsiveness.
最近，在作为哮喘遗传学合作研究（CSGA）一部分招募的白种人家系的全基因组筛查中，我们获得了证据，表明Der p 1特异性IgE抗体与6号染色体p21（HLA - D区域）上的标记之间存在连锁关系。
通过免疫印迹分析检测针对不同尘螨（Der p）多肽的特异性IgE抗体，并在针对每种不同Der p多肽的特异性IgE反应性与6号染色体p21上的标记之间进行传递/不平衡检验（TDT），以更好地阐明HLA - D基因的遗传贡献。
我们研究了参与CSGA的45个白种人家系中的299名个体。对ACCESS免疫测定显示针对Der p粗过敏原的特异性IgE抗体升高（> -0.5 log IU/mL）的137名个体的血清样本进行免疫印迹分析。在针对12种不同Der p多肽中的每一种的特异性IgE抗体的存在与6号染色体p21上的4个多态性标记之间进行TDT。
D6S1281的196 bp等位基因和DQCAR的104 bp等位基因向针对特定Der p多肽（120 kd、55 kd、45 kd或37 kd）的特异性IgE反应者的传递显著过量。相比之下，D6S1281的200 bp等位基因和D6S291的204 bp等位基因向针对特定Der p多肽（120 kd、90 kd、52 kd或45 kd）的特异性IgE反应者的传递显著减少。在进行多重比较校正后，杂合子父母中偏离预期50%传递的情况具有统计学意义。
本研究支持了我们之前的发现，即6号染色体p21（HLA - D区域）上的基因可能影响该白种人群中Der p特异性IgE反应性的表达。然而，我们的结果揭示了HLA - D基因对Der p特异性IgE反应性进行遗传调控的复杂性，表明非HLA基因座以及可能的环境因素对Der p特异性IgE反应性的发展有强烈影响。
