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

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

机构地区：[1]Mucosal Immunology and Biology Research Center, Mass General Hospital for Children, Boston, MA 02115, United States [2]Center for Celiac Research and Treatment, Mass General Hospital for Children, Boston, MA 02115, United States [3]Department of Pediatric Gastroenterology and Nutrition, Mass General Hospital for Children, Boston, MA 02114, United States [4]Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States

出　　处：《World Journal of Diabetes》2019年第3期189-199,共11页世界糖尿病杂志（英文版）（电子版）

基　　金：Supported by The Center for Celiac Research and Treatment,The Nutrition Obesity Research Center at Harvard,No.P30-DK04561;to MML and RAB;The Harvard Clinical and Translational Science Center,the Harvard Catalyst,NCRR and NCATS,NIH Award,No.UL1 TR001102

摘　　要：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.BACKGROUND Patients with type 1 diabetes(T1 D) 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 T1 D and their FDRs.Additionally, we aimed at identifying predictors associated with an increased risk of developing CDA in patients with T1 D and their family members.METHODS We obtained clinical information and blood samples from 1027 participants(302 with T1 D 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 T1 D and for FDRs of subjects with T1 D.RESULTS Implementation of a screening program increased the frequency of CDA by 2-fold in participants with T1 D and 2.8-fold in their FDRs. Multivariate analysis found that, in participants with T1 D, having both DR7-DQ2 and DR4-DQ8 was associated with an increased frequency of CDA. In FDRs of T1 D 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 T1 D 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 T1 D.

关 键 词：Screening GLUTEN Diabetic COELIAC HAPTOGLOBIN Human LEUKOCYTE antigen 

分 类 号：R[医药卫生]