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摩洛哥人 HLA 二类分子与 1 型糖尿病的基于家系的关联研究。

Family-based association study of HLA class II with type 1 diabetes in Moroccans.

作者信息

Drissi Bourhanbour A, Benseffaj N, Ouadghiri S, Razine R, Touzani A, Belafraj A, Essakalli M

机构信息

UPR d'immunologie, faculté de médecine et de pharmacie, Rabat Institut, avenue Mohamed Belarbi El Alaoui, BP 6203, 10000 Rabat, Morocco; Unité d'immunologie, service de transfusion sanguine et d'hémovigilance, hôpital d'enfants-Rabat, Rabat Institut, CHU Ibn-Sina, rue Lamfadel Cherkaoui, BP 6527, Rabat, Morocco.

UPR d'immunologie, faculté de médecine et de pharmacie, Rabat Institut, avenue Mohamed Belarbi El Alaoui, BP 6203, 10000 Rabat, Morocco; Unité d'immunologie, service de transfusion sanguine et d'hémovigilance, hôpital d'enfants-Rabat, Rabat Institut, CHU Ibn-Sina, rue Lamfadel Cherkaoui, BP 6527, Rabat, Morocco.

出版信息

Pathol Biol (Paris). 2015 Apr;63(2):80-4. doi: 10.1016/j.patbio.2014.12.001. Epub 2014 Dec 30.

Abstract

BACKGROUND

The T1D is a multifactorial disease; with a strong genetic control. The human leukocyte antigen (HLA) system plays a crucial role in the autoimmune process leading to childhood diabetes. About 440,000 of the childhood population of the world (1.8 billion children under 14 years of age), have type 1 diabetes, and each year an additional 70,000 develop this disorder. The objective of this study was to investigate the distribution of HLA class II in Moroccan families of diabetic children to identify susceptibility alleles of the Moroccan population.

SUBJECTS AND METHODS

We included in this study, Moroccan families who have at least one child with T1D. The age of onset of diabetes was less than 15 years. HLA class II (DRB1* and DQB1*) was carried out by molecular biology techniques (PCR-SSP and PCR-SSO). The FBAT test (family-based association test) was used to highlight the association between T1D and the HLA-DRB1* and -DQB1* polymorphism.

RESULTS

The association of HLA class II (DRB1*, DQB1*) in type 1 diabetes was analyzed in fifty-one Moroccan families, including 90 diabetics. The results revealed that the most susceptible haplotypes are the DRB103:01-DQB102:01, DRB104:05-DQB103:02 (Z=3.674, P=0.000239; Z=2.828, P=0.004678, respectively). And the most protective haplotype is the DRB115-DQB106.

CONCLUSION

This is the first family-based association study searching for an association between HLA class II and T1D in a Moroccan population. Despite the different ethnic groups forming Morocco, Moroccan diabetics share the most susceptible and protective HLA haplotypes with other Caucasians populations, specifically the European and Mediterranean populations.

摘要

背景

1型糖尿病(T1D)是一种多因素疾病,受强大的基因控制。人类白细胞抗原(HLA)系统在导致儿童糖尿病的自身免疫过程中起关键作用。世界儿童人口(14岁以下的18亿儿童)中约有44万患有1型糖尿病,且每年还有7万新增病例。本研究的目的是调查摩洛哥糖尿病儿童家庭中HLA II类分子的分布,以确定摩洛哥人群的易感等位基因。

对象与方法

本研究纳入了至少有一名患T1D儿童的摩洛哥家庭。糖尿病发病年龄小于15岁。采用分子生物学技术(PCR-SSP和PCR-SSO)检测HLA II类分子(DRB1和DQB1)。使用FBAT检验(基于家系的关联检验)来突出T1D与HLA-DRB1和-DQB1多态性之间的关联。

结果

在51个摩洛哥家庭(包括90名糖尿病患者)中分析了HLA II类分子(DRB1*、DQB1*)与1型糖尿病的关联。结果显示,最易感单倍型是DRB103:01-DQB102:01、DRB104:05-DQB103:02(Z分别为3.674,P = 0.000239;Z为2.828,P = 0.004678)。最具保护作用的单倍型是DRB115-DQB106。

结论

这是在摩洛哥人群中首次进行的基于家系的关联研究,旨在寻找HLA II类分子与T1D之间的关联。尽管摩洛哥由不同种族组成,但摩洛哥糖尿病患者与其他高加索人群,特别是欧洲和地中海人群,共享最易感和最具保护作用的HLA单倍型。

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