Zamani M, Modares-Sadegi M, Shirvani F, Zamani H, Emami M H
Faculty of Medicine, Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran; Department of Neurogenetics, Iranian Centre of Neurological Research, Tehran University of Medical Sciences, Tehran, Iran.
Int J Immunogenet. 2014 Aug;41(4):312-7. doi: 10.1111/iji.12128. Epub 2014 Jun 11.
Coeliac disease (CD) is a highly prevalent autoimmune disorder that is triggered by the ingestion of wheat gluten and related proteins in genetically susceptible individuals. The CD is associated with human leucocyte antigen (HLA) genes particularly with HLA-DQ alleles encoding HLA-DQ2 and DQ8 proteins. To define risk and severity alleles for CD, a total of 120 definite CD patients and 100 healthy controls were genotyped for HLA-DQB1 gene. HLA-DQB1 genotyping was performed in all patients and controls using PCR-SSP technique, and to evaluate the clinical relevance of testing for HLA-DQB1 and determining absolute risk of disease, prevalence-corrected positive predictive value and prevalence-corrected negative predictive value (PcPPV and PcNPV) were calculated. Our results for a first time show that DQB102:00 and DQB103:02 alleles and DQB102:01/03:02 genotype very significantly associated with increased risk of patients with CD, and DQB103:01,4 allele provides protection against CD in Iranian patients. Furthermore, the PcPPV for DQB02:01 and 03:02 alleles in CD were 0.014 and 0.012, respectively, and the highest absolute risk presented by DQB0201/0302 genotype (PcPPV = 0.079) and 98% of patients with CD carried DQB102:01/x or DQB103:02/x genotype. The results also clearly demonstrated that the DQB102:01 allele significantly associated with severity of CD, while DQB103:02 allele associated with mild form of CD. These results suggest that clinically suspected individuals for CD and first-degree relatives of patients with CD to be screened for HLA-DQB0201 and DQB0302 alleles for possible early diagnosis and treatments.
乳糜泻（CD）是一种高度流行的自身免疫性疾病，在遗传易感个体中，由摄入小麦麸质及相关蛋白质引发。CD与人类白细胞抗原（HLA）基因相关，特别是与编码HLA - DQ2和DQ8蛋白的HLA - DQ等位基因有关。为确定CD的风险和严重程度等位基因，对120例确诊的CD患者和100名健康对照进行了HLA - DQB1基因分型。所有患者和对照均采用PCR - SSP技术进行HLA - DQB1基因分型，并计算患病率校正后的阳性预测值和患病率校正后的阴性预测值（PcPPV和PcNPV），以评估检测HLA - DQB1及确定疾病绝对风险的临床相关性。我们的结果首次表明，DQB102:00和DQB103:02等位基因以及DQB102:01/03:02基因型与CD患者风险增加显著相关，而DQB103:01、4等位基因对伊朗患者的CD具有保护作用。此外，CD中DQB02:01和03:02等位基因的PcPPV分别为0.014和0.012，DQB0201/0302基因型呈现的绝对风险最高（PcPPV = 0.079），98%的CD患者携带DQB102:01/x或DQB103:02/x基因型。结果还清楚地表明，DQB102:01等位基因与CD的严重程度显著相关，而DQB103:02等位基因与CD的轻度形式相关。这些结果表明，对于临床疑似CD的个体以及CD患者的一级亲属，应筛查HLA - DQB0201和DQB0302等位基因，以便可能进行早期诊断和治疗。
