斯洛伐克人群中HLA - DRB1和HLA - DQB1等位基因与多发性硬化症遗传易感性的关联。

The association of HLA-DRB1 and HLA-DQB1 alleles with genetic susceptibility to multiple sclerosis in the Slovak population.

作者信息

Michalik Jozef, Čierny Daniel, Kantorová Ema, Kantárová Daniela, Juraj Javor, Párnická Zuzana, Kurča Egon, Dobrota Dušan, Lehotský Ján

机构信息

1 Clinic of Neurology, Jessenius Faculty of Medicine and University Hospital in Martin, Comenius University in Bratislava , Martin, Slovakia.

出版信息

Neurol Res. 2015;37(12):1060-7. doi: 10.1080/01616412.2015.1115212. Epub 2016 Jan 8.

DOI:10.1080/01616412.2015.1115212

PMID:26744784

Abstract

OBJECTIVE

The aim of the present study was to assess the association between HLA-DRB1 and -DQB1 allele groups with the genetic predisposition to multiple sclerosis (MS) in the Caucasian Central European Slovak population.

METHODS

A total of 282 unrelated patients with sporadic MS were enrolled in this case-control study. HLA-DRB1 and HLA-DQB1 allele groups were genotyped using a polymerase chain reaction with sequence-specific primers. The DRB1 and DQB1 allele carrier frequencies, genotypes and haplotype frequencies were compared between MS cases and healthy controls.

RESULTS

Positive association with MS was found for alleles HLA-DRB115 (OR = 3.64; Pcor = 6.9x10-11), DRB103 (after elimination of carriers of DRB115, OR = 2.8; Pcor = 0.0029), DQB106 (OR = 1.99; Pcor = 7.0x10-4), genotypes HLA-DRB115/15 (OR = 7.6; Pcor = 0.001) and DQB106/06 (OR = 3.81; Pcor = 4.0x10-4) and for haplotype DRB115-DQB106 (OR = 3.03; Pcor = 0.001). Carriage of alleles DRB107 (OR = 0.53; Pcor = 0.04), DRB113 (OR = 0.39; Pcor = 4.0x10-4), DQB103 (OR = 0.46; Pcor = 1.0x10-4), genotypes HLA-DRB113/11 (OR = 0.12; Pcor = 0.004), DQB105/03 (OR = 0.39; Pcor = 0.035), DQB103/03 (OR = 0.38; Pcor = 0.029) and haplotypes DRB113-DQB106 (OR = 0.47; Pcor = 0.0128) and DRB111-DQB1*03 (OR = 0.58; Pcor = 0.0352) was found to be protective against MS development.

DISCUSSION

This is the first study performed to analyse the association of HLA-DRB1/DQB1 with susceptibility to MS in Slovakia. The results of our study confirm that HLA class II alleles, genotypes and haplotypes are associated with MS risk.

摘要

目的

本研究旨在评估在中欧斯洛伐克白种人群中，HLA - DRB1和 - DQB1等位基因组与多发性硬化症（MS）遗传易感性之间的关联。

方法

本病例对照研究共纳入282例散发性MS的非亲属患者。采用序列特异性引物聚合酶链反应对HLA - DRB1和HLA - DQB1等位基因组进行基因分型。比较MS病例组和健康对照组之间的DRB1和DQB1等位基因携带频率、基因型和单倍型频率。

结果

发现与MS呈正相关的等位基因有HLA - DRB115（比值比[OR]=3.64；校正P值[Pcor]=6.9×10⁻¹¹）、DRB103（排除DRB115携带者后，OR = 2.8；Pcor = 0.0029）、DQB106（OR = 1.99；Pcor = 7.0×10⁻⁴），基因型有HLA - DRB115/15（OR = 7.6；Pcor = 0.001）和DQB106/06（OR = 3.81；Pcor = 4.0×10⁻⁴），单倍型有DRB115 - DQB106（OR = 3.03；Pcor = 0.001）。发现携带等位基因DRB107（OR = 0.53；Pcor = 0.04）、DRB113（OR = 0.39；Pcor = 4.0×10⁻⁴）、DQB103（OR = 0.46；Pcor = 1.0×10⁻⁴），基因型有HLA - DRB113/11（OR = 0.12；Pcor = 0.004）、DQB105/03（OR = 0.39；Pcor = 0.035）、DQB103/03（OR = 0.38；Pcor = 0.029）以及单倍型DRB113 - DQB106（OR = 0.47；Pcor = 0.0128）和DRB111 - DQB1*03（OR =