Muazzam Ambreen Gul, Mansoor Atika, Ali Lubna, Siddiqi Saima, Hameed Abdul, Ajmal Muhammad, Mazhar Kehkashan
Arthritis Res Ther. 2013 Aug 22;15(4):R95. doi: 10.1186/ar4275.
Rheumatoid arthritis is an autoimmune disease with poorly understood pathophysiology. Genetic components of disease etiology, especially human leukocyte antigen (HLA) associations, are well known. Ethnic differences account for a number of variations in disease association with the HLA locus and there seem to be differences in various studies regarding its genetic predisposition. This study was aimed at determining the contribution of DRB1 and DQB1 components of HLA class II in rheumatoid arthritis in a Pakistani cohort.
For this study, 110 patients and 120 healthy controls from the same geographical area and matched ethnicity were enrolled. Blood DNA was isolated from all the subjects and HLA alleles were typed following allele specific amplification. Subsequently, haplotypes were generated and allelic and haplotype distribution frequencies were compared among the patients and controls using χ² and Arlequin software. The data obtained by this analysis were also compared with other reported associations found in the Pakistani population by meta-analysis.
HLA allelic status was determined among the patients and controls from the same geographical area to account for differences in ethnicity and environmental factors. Significant associations were found for alleles as well as haplotypes among the patients of rheumatoid arthritis. DRB110, DQB105 and DQB1602 were found to be associated with disease susceptibility, whereas DRB111 and DQB102 had protective effect against the disease. Similarly, haplotype DRB110-DQB105 was associated disease risk, whereas DRB107-DQB102 and DRB111-DQB1*0301 had a protective effect.
There is a significant DRB1and DQB1 allele and haplotype association with rheumatoid arthritis susceptibility and protection.
类风湿性关节炎是一种自身免疫性疾病，其病理生理学尚不清楚。疾病病因的遗传成分，尤其是人类白细胞抗原（HLA）关联，是众所周知的。种族差异导致了与HLA基因座相关疾病的多种变异，并且在关于其遗传易感性的各种研究中似乎存在差异。本研究旨在确定巴基斯坦队列中HLA II类的DRB1和DQB1成分在类风湿性关节炎中的作用。
在本研究中，招募了来自同一地理区域且种族匹配的110例患者和120名健康对照。从所有受试者中分离出血液DNA，并通过等位基因特异性扩增对HLA等位基因进行分型。随后，生成单倍型，并使用χ²和Arlequin软件比较患者和对照之间的等位基因和单倍型分布频率。通过荟萃分析，将该分析获得的数据也与在巴基斯坦人群中发现的其他报道关联进行比较。
确定了来自同一地理区域的患者和对照之间的HLA等位基因状态，以解释种族和环境因素的差异。在类风湿性关节炎患者中发现等位基因以及单倍型存在显著关联。发现DRB110、DQB105和DQB1602与疾病易感性相关，而DRB111和DQB102对该疾病具有保护作用。同样，单倍型DRB110-DQB105与疾病风险相关，而DRB107-DQB102和DRB111-DQB1*0301具有保护作用。
DRB1和DQB1等位基因及单倍型与类风湿性关节炎易感性和保护性之间存在显著关联。
