Gu X F, Larger E, Clauser E, Bessaoud K, Krishnamoorthy R, Elion J, Assan R
Service de Diabétologie, Hôpital Bichat, Paris, France.
Diabetes Res. 1991 Aug;17(4):189-97.
Some alleles of the HLA-DQB1 and DQA1 loci are preferentially associated with susceptibility to type 1 (insulin-dependent) diabetes mellitus (IDDM). Analysis of the HLA-DQ genetic profile may therefore become important for the screening of subjects at risk of IDDM. However ethnic variations in the genetic profile can occur and require background knowledge of the HLA-DQ allelic distribution before screening campaigns. In the present work, HLA-DQA1 and DQB1 genes have been analyzed, after PCR amplification of the genomic DNA, in French and Algerian control subjects (a total of 148) and diabetic patients (a total of 107). Allelic distributions have been investigated in view of a) possible inter-ethnic differences; b) identification of risk and protective alleles and c) the prevalence of DQB1 aspartate 57 negative and DQA1 arginine 52 positive alleles in control and diabetic groups. The DQB1 allelic distribution was similar in both control groups; alleles negative for aspartate at position 57 were 48% in French and 50% in Algerian. In both diabetic groups, the prevalence of alleles negative for aspartate at position 57 was significantly higher: 91% (French) and 81% (Algerian) (p less than 0.001). A majority of patients were homozygote for DQB1 Asp 57 negativity: 83% (French) and 63% (Algerian). The highest relative risk was associated with HLA-DQB1 0201/0302 heterozygosity. The HLA-DQA1 allelic distribution was also similar in French and Algerian controls. Alleles positive for arginine (ARG+) at position 52 were 50% (French) and 57% (Algerian) of controls. In both diabetic groups the prevalence of alleles positive for arginine at position 52 was significantly higher: 78% (French) and 84% (Algerian).(ABSTRACT TRUNCATED AT 250 WORDS)
HLA - DQB1和DQA1基因座的某些等位基因与1型(胰岛素依赖型)糖尿病(IDDM)易感性优先相关。因此,HLA - DQ基因谱分析对于筛查IDDM风险受试者可能变得很重要。然而,基因谱存在种族差异,在筛查之前需要了解HLA - DQ等位基因分布的背景知识。在本研究中,对法国和阿尔及利亚的对照受试者(共148名)和糖尿病患者(共107名)的基因组DNA进行PCR扩增后,分析了HLA - DQA1和DQB1基因。鉴于a)可能存在的种族间差异;b)识别风险和保护性等位基因;c)对照和糖尿病组中DQB1天冬氨酸57阴性和DQA1精氨酸52阳性等位基因的患病率,对等位基因分布进行了研究。两个对照组中DQB1等位基因分布相似;57位天冬氨酸阴性的等位基因在法国人为48%,在阿尔及利亚人为50%。在两个糖尿病组中,57位天冬氨酸阴性的等位基因患病率显著更高:91%(法国人)和81%(阿尔及利亚人)(p小于0.001)。大多数患者为DQB1天冬氨酸57阴性纯合子:83%(法国人)和63%(阿尔及利亚人)。最高相对风险与HLA - DQB1 0201/0302杂合性相关。法国和阿尔及利亚对照组中HLA - DQA1等位基因分布也相似。52位精氨酸(ARG +)阳性的等位基因在法国对照组中占50%,在阿尔及利亚对照组中占57%。在两个糖尿病组中,52位精氨酸阳性的等位基因患病率显著更高:78%(法国人)和84%(阿尔及利亚人)。(摘要截短于250字)