Tinto Nadia, Cola Arturo, Piscopo Chiara, Capuano Marina, Galatola Martina, Greco Luigi, Sacchetti Lucia
Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Naples, Italy; CEINGE-Advanced Biotechnology, s. c. a r. l., Naples, Italy.
Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Naples, Italy; Department of Translational Medical Sciences, Section of Pediatrics, University of Naples "Federico II", Naples, Italy.
PLoS One. 2015 Sep 23;10(9):e0138324. doi: 10.1371/journal.pone.0138324. eCollection 2015.
Celiac disease (CD) has a strong genetic component mainly due to HLA DQ2/DQ8 encoding genes. However, a minority of CD patients are DQ2/DQ8-negative. To address this issue, we retrospectively characterized HLA haplotypes in 5,535 subjects at risk of CD (either relatives of CD patients or subjects with CD-like symptoms) referred to our center during a 10-year period.
We identified loci DQA1/DQB1/DRB1 by sequence-specific oligonucleotide-PCR and sequence-specific primer-PCR; anti-transglutaminase IgA/IgG and anti-endomysium IgA by ELISA and indirect immunofluorescence, respectively.
We diagnosed CD in 666/5,535 individuals, 4.2% of whom were DQ2/DQ8-negative. Interestingly, DQ7 was one of the most abundant haplotypes in all CD patients and significantly more frequent in DQ2/DQ8-negative (38%) than in DQ2/DQ8-positive CD patients (24%) (p<0.05).
Our data lend support to the concept that DQ7 represents an additive or independent CD risk haplotype with respect to DQ2/DQ8 haplotypes but this finding should be verified in other large CD populations.
乳糜泻(CD)具有很强的遗传因素,主要归因于编码HLA DQ2/DQ8的基因。然而,少数CD患者为DQ2/DQ8阴性。为解决这一问题,我们回顾性分析了10年间转诊至本中心的5535名有CD风险的受试者(CD患者的亲属或有CD样症状的受试者)的HLA单倍型。
我们通过序列特异性寡核苷酸PCR和序列特异性引物PCR鉴定DQA1/DQB1/DRB1位点;分别通过酶联免疫吸附测定法(ELISA)和间接免疫荧光法检测抗转谷氨酰胺酶IgA/IgG和抗肌内膜IgA。
我们在5535名个体中诊断出666例CD,其中4.2%为DQ2/DQ8阴性。有趣的是,DQ7是所有CD患者中最常见的单倍型之一,在DQ2/DQ8阴性的CD患者中(38%)比在DQ2/DQ8阳性的CD患者中(24%)更为常见(p<0.05)。
我们的数据支持以下观点,即相对于DQ2/DQ8单倍型,DQ7代表一种附加的或独立的CD风险单倍型,但这一发现应在其他大型CD人群中得到验证。