针对1型糖尿病患者及其家庭成员进行乳糜泻自身免疫性疾病发展预测的靶向基因分型。

Targeted genotyping for the prediction of celiac disease autoimmunity development in patients with type 1 diabetes and their family members.

作者信息

Leonard Maureen M, Camhi Stephanie, Kenyon Victoria, Betensky Rebecca A, Sturgeon Craig, Yan Shu, Fasano Alessio

机构信息

Mucosal Immunology and Biology Research Center, Mass General Hospital for Children, Boston, MA 02115, United States.

Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States.

出版信息

World J Diabetes. 2019 Mar 15;10(3):189-199. doi: 10.4239/wjd.v10.i3.189.

DOI:10.4239/wjd.v10.i3.189

PMID:30891154

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6422857/

Abstract

BACKGROUND

Patients with type 1 diabetes (T1D) and their first-degree relatives (FDRs) have an increased risk of developing celiac disease (CD) compared to the general population. This is largely explained by the shared association with major histocompatibility class II human leukocyte antigen (HLA) DQ2 and/or DQ8 between the two disease states.

AIM

To describe the frequency of CD autoimmunity (CDA) and the distribution of HLA and haptoglobin genotypes in patients with T1D and their FDRs. Additionally, we aimed at identifying predictors associated with an increased risk of developing CDA in patients with T1D and their family members.

METHODS

We obtained clinical information and blood samples from 1027 participants (302 with T1D and 725 FDRs) over a five-year period. Samples were tested for autoantibodies associated with CD, HLA-DQ alleles, and haptoglobin genotype. We fit univariate and multiple logistic regression models for CDA separately for subjects with T1D and for FDRs of subjects with T1D.

RESULTS

Implementation of a screening program increased the frequency of CDA by 2-fold in participants with T1D and 2.8-fold in their FDRs. Multivariate analysis found that, in participants with T1D, having both DR7-DQ2 and DR4-DQ8 was associated with an increased frequency of CDA. In FDRs of T1D patients, reported CD in the family was associated with an increased frequency of CDA during screening. Haptoglobin 2 genotype was not associated with developing CDA in the multivariate analysis.

CONCLUSION

Patients with T1D and their FDRs have a high frequency of CDA. Carrying both DR7-DQ2 and DR4-DQ8 was associated with development of CDA in patients with T1D.

摘要

背景

与普通人群相比，1型糖尿病（T1D）患者及其一级亲属（FDRs）患乳糜泻（CD）的风险增加。这在很大程度上是由于两种疾病状态与主要组织相容性复合体II类人类白细胞抗原（HLA）DQ2和/或DQ8存在共同关联。

目的

描述T1D患者及其FDRs中CD自身免疫（CDA）的频率以及HLA和触珠蛋白基因型的分布。此外，我们旨在确定与T1D患者及其家庭成员发生CDA风险增加相关的预测因素。

方法

在五年期间，我们从1027名参与者（302名T1D患者和725名FDRs）那里获取了临床信息和血样。对样本进行与CD相关的自身抗体、HLA - DQ等位基因和触珠蛋白基因型检测。我们分别为T1D患者和T1D患者的FDRs拟合了CDA的单变量和多变量逻辑回归模型。

结果

实施筛查项目使T1D参与者中CDA的频率增加了2倍，其FDRs中增加了2.8倍。多变量分析发现，在T1D参与者中，同时具有DR7 - DQ2和DR4 - DQ8与CDA频率增加相关。在T1D患者的FDRs中，家族中报告有CD与筛查期间CDA频率增加相关。在多变量分析中，触珠蛋白2基因型与发生CDA无关。