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阿尔及利亚1型糖尿病家族中的HLA DQA1和DQB1研究。

HLA DQA1 and DQB1 study in Algerian type 1 diabetes families.

作者信息

Beressi J P, Djoulah S, Khalil I, Benhamamouch S, Bessaoud K, Touhami M, Hors J, Deschamps I

机构信息

INSERM U30, Hôpital Necker, Paris, France.

出版信息

Diabete Metab. 1992 Nov-Dec;18(6):451-8.

PMID:1297602
Abstract

The distribution of HLA class II alleles associated with insulin-dependent diabetes mellitus (Type 1) in the Algerian population is poorly known. We have typed 36 Algerian Type 1 diabetic probands and their families using DQA1 and DQB1 oligonucleotide probes. Fifty-nine parental haplotypes non transmitted to diabetic offspring served as controls. The frequencies of DQA1 and DQB1 alleles and haplotypes and their associations with Type 1 diabetes were, except minor differences, similar to those reported in French. Susceptibility DQA1 (Arg52+) and DQB1 (Asp57-) alleles were significantly increased among patients versus controls (90% vs 53%, RR = 8.4, p < 10(-6), and 94% vs 64%, RR = 9.4, p < 10(-5), respectively). 85% of Type 1 diabetics versus 34% of control haplotypes were either DR3DQw2 or DR4DQw8 susceptibility haplotypes (DQA1 Arg52+, DQB1 Asp57-) (RR = 10.8, p < 10(-7). 75% of the probands vs 14% of the controls (RR = 18, p < 10(-5)) and 73% of affected siblings versus 24% of unaffected siblings (RR = 8.4, p < 0.02) possessed a genotype composed of these two susceptibility haplotypes in the homozygous or heterozygous state. 42% of the probands were DR3DQw2/DR4DQw8, corresponding to Hardy-Weinberg expectations. The lack of excess of heterozygotes could be due to the consanguine families in this sample, as among the patients with consanguine parents the frequency of DR3, 4 heterozygotes was lower (27% vs 48% in non-consanguine patients, NS) and that of DR3 homozygotes increased (45% vs 12%, respectively, p < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

阿尔及利亚人群中与胰岛素依赖型糖尿病(1型)相关的人类白细胞抗原II类等位基因的分布情况鲜为人知。我们使用DQA1和DQB1寡核苷酸探针,对36名阿尔及利亚1型糖尿病先证者及其家族进行了分型。59个未传递给糖尿病后代的亲代单倍型用作对照。除了一些细微差异外,DQA1和DQB1等位基因及单倍型的频率及其与1型糖尿病的关联,与法国报道的情况相似。与对照组相比,患者中易感性DQA1(Arg52 +)和DQB1(Asp57 -)等位基因显著增加(分别为90%对53%,相对危险度RR = 8.4,p < 10^(-6);以及94%对64%,RR = 9.4,p < 10^(-5))。85%的1型糖尿病患者与34%的对照单倍型为DR3DQw2或DR4DQw8易感性单倍型(DQA1 Arg52 +,DQB1 Asp57 -)(RR = 10.8,p < 10^(-7))。75%的先证者与14%的对照者(RR = 18,p < 10^(-5))以及73%的患病同胞与24%的未患病同胞(RR = 8.4,p < 0.02)拥有由这两种易感性单倍型组成的纯合或杂合基因型。4 . 2%的先证者为DR3DQw2 / DR4DQw8,符合哈迪 - 温伯格预期。杂合子缺乏过剩情况可能归因于该样本中的近亲家族,因为在父母为近亲的患者中,DR3、4杂合子的频率较低(非近亲患者中为48%,近亲患者中为27%,无显著差异),而DR3纯合子的频率增加(分别为45%对12%,p < 0.03)。(摘要截短于250字)

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