Nieto A, Blanco Quirós A, Arranz E, Alonso Franch M, Garrote J A, Calvo C
Department of Pediatrics, Georgetown University, Washington, D.C., USA.
J Investig Allergol Clin Immunol. 1995 Jul-Aug;5(4):209-15.
The familial incidence of celiac disease (CD) confirms its genetic basis, although acquired factors are also involved. Many authors have reported a linkage between celiac disease and HLA antigens, but there are differences which depend on geographical areas, and nowadays the study must be done at the genetic level. Thirty-eight celiac children and 52 normal controls were included in this study. All individuals were chosen from the Castilla and Leon area. We used the reverse ¿dot block¿ technique, using sequence-specific oligonucleotide DNA probes (Cetus, USA) to determine the HLA-DQA1 alleles in DNA samples previously amplified by PCR (polymerase chain reaction). The different frequency of alleles in patients and controls was assessed by 3 statistical tests: chi square (chi(2)), relative risk (RR) and etiologic fraction (EF). A very high frequency of DQA10201 (chi(2):p <0.0001) and DQA10501 (chi(2): p <0.0001) alleles was observed in patients; all but one (97%) had the DQA10501 allele vs. 40% of controls (RR: 37.00; EF: 0.955). The DQA10201 allele also had a high prevalence in celiacs (58%)(RR: 1.375: EF:0.438). The DQA101 allele was only found in 10.5% of patients compared to 79% of controls (chi(2): p <0.0001) and the DQA103 allele was also decreased in celiacs. There was only one celiac girl without the DQA10501 allele. She had no other clinical or serological differences, as compared to the other patients. In the study of allele subtypes, among the DQA101 allele, 50% of patients were positive for DQA1101 and the remaining 50% had DQA10102, but none of the individuals were positive for DQA10103. Among normal controls, 32 individuals (61.5%) expressed the DQA10102 subtype, 15 (28.9%) the DQA10101 subtype and 5 (9.6%) the DQA10103 subtype. All positive cases for DQA1-05 belong to the DQA1 0501 subtype, in both celiac and control groups. There were 10 possible combinations of HLA-DQA1 genes, but we found a very unequal distribution in both celiacs and controls. Only 4 genotypes were found in patients (DQA101/10501, DQA1* 0201/10501, DQA103/10501 and DQA10501/10501) and 8 in controls. The DQA10201/1*-0501 genotype was the most discordant, being positive in 55.3% of patients vs. 3.8% of controls (chi2:p < 0.001; RR: 1.235; EF:0.534). None of the 90 individuals studied expressed the DQA1031103 genotype. The DQA10201/103 genotype was not shown by any control and by only 1 celiac patient. It is noteworthy that the DQA10201/10501 genotype was more frequent than the homozygous genotype DQA10501/10501. Our results do not suggest a dosage effect for the DQA1*0501 allele. The determination of the HLA-DQA1 gene is a helpful tool for the screening of individuals with a high risk of being celiacs.
乳糜泻（CD）的家族发病率证实了其遗传基础，尽管也涉及后天因素。许多作者报道了乳糜泻与HLA抗原之间的联系，但存在因地理区域而异的差异，如今必须在基因水平上进行研究。本研究纳入了38名乳糜泻儿童和52名正常对照。所有个体均选自卡斯蒂利亚-莱昂地区。我们使用反向“点杂交”技术，采用序列特异性寡核苷酸DNA探针（美国赛特斯公司）来确定先前通过聚合酶链反应（PCR）扩增的DNA样本中的HLA-DQA1等位基因。通过三种统计检验评估患者和对照中等位基因的不同频率：卡方检验（chi(2)）、相对风险（RR）和病因分数（EF）。在患者中观察到DQA10201（chi(2)：p <0.0001）和DQA10501（chi(2)：p <0.0001）等位基因的频率非常高；除一名患者外（97%），所有患者都有DQA10501等位基因，而对照中为40%（RR：37.00；EF：0.955）。DQA10201等位基因在乳糜泻患者中也有较高的患病率（58%）（RR：1.375；EF：0.438）。DQA101等位基因仅在10.5%的患者中发现，而对照中为79%（chi(2)：p <0.0001），DQA103等位基因在乳糜泻患者中也减少。只有一名没有DQA10501等位基因的乳糜泻女孩。与其他患者相比，她没有其他临床或血清学差异。在等位基因亚型研究中，在DQA101等位基因中，50%的患者DQA1101呈阳性，其余50%有DQA10102，但没有个体DQA10103呈阳性。在正常对照中，32名个体（61.5%）表达DQA10102亚型，15名（28.
