Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study

被引：31

作者：

Torn, Carina ^{[1
]}

Liu, Xiang ^{[2
]}

Hagopian, William ^{[3
]}

Lernmark, Ake ^{[1
]}

Simell, Olli ^{[4
]}

Rewers, Marian ^{[5
]}

Ziegler, Anette-G ^{[6
,7
,8
]}

Schatz, Desmond ^{[9
]}

Akolkar, Beena ^{[10
]}

Onengut-Gumuscu, Suna ^{[11
]}

Chen, Wei-Min ^{[11
]}

Toppari, Jorma ^{[4
,12
,13
]}

Mykkanen, Juha ^{[4
,12
,13
]}

Ilonen, Jorma ^{[12
,13
]}

Rich, Stephen S. ^{[11
]}

She, Jin-Xiong ^{[14
]}

Sharma, Ashok ^{[14
]}

Steck, Andrea ^{[5
]}

Krischer, Jeffrey ^{[2
]}

机构：

[1] Lund Univ, Dept Clin Sci, CRC, Malmo, Sweden

[2] Univ S Florida, Morsani Coll Med, Hlth Informat Inst, Tampa, FL USA

[3] Pacific Northwest Diabet Res Inst, Seattle, WA USA

[4] Turku Univ Hosp, Dept Pediat, FIN-20520 Turku, Finland

[5] Univ Colorado, Barbara Davis Ctr Childhood Diabet, Aurora, CO USA

[6] Helmholtz Zentrum, Diabet Res Inst, Munich, Germany

[7] Tech Univ Munich, Klinikum Rechts Isar, Neuherberg, Germany

[8] Forschergrp Diabet eV, Neuherberg, Germany

[9] Univ Florida, Dept Pediat, Gainesville, FL USA

[10] NIDDK, Bethesda, MD 20892 USA

[11] Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA USA

[12] Univ Turku, Dept Phys, SF-20500 Turku, Finland

[13] Univ Turku, Dept Pediat, Turku, Finland

[14] Augusta Univ, Med Coll Georgia, Ctr Biotechnol & Genom Med, Augusta, GA USA

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

关键词：

ANTIBODY STANDARDIZATION PROGRAM; GLUTAMIC-ACID DECARBOXYLASE; CLASS-I; RISK; HLA; ACTIVATION; ASSOCIATION; ASSAYS; SUSCEPTIBILITY; LOCALIZATION;

D O I：

10.1038/srep27887

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A total of 15 SNPs within complement genes and present on the ImmunoChip were analyzed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. A total of 5474 subjects were followed from three months of age until islet autoimmunity (IA: n = 413) and the subsequent onset of type 1 diabetes (n = 115) for a median of 73 months (IQR 54-91). Three SNPs within ITGAM were nominally associated (p < 0.05) with IA: rs1143678 [Hazard ratio; HR 0.80; 95% CI 0.66-0.98; p = 0.032], rs1143683 [HR 0.80; 95% CI 0.65-0.98; p = 0.030] and rs4597342 [HR 1.16; 95% CI 1.01-1.32; p = 0.041]. When type 1 diabetes was the outcome, in DR3/4 subjects, there was nominal significance for two SNPs: rs17615 in CD21 [HR 1.52; 95% CI 1.05-2.20; p = 0.025] and rs4844573 in C4BPA [HR 0.63; 95% CI 0.43-0.92; p = 0.017]. Among DR4/4 subjects, rs2230199 in C3 was significantly associated [HR 3.20; 95% CI 1.75-5.85; p = 0.0002, uncorrected] a significance that withstood Bonferroni correction since it was less than 0.000833 (0.05/60) in the HLA-specific analyses. SNPs within the complement genes may contribute to IA, the first step to type 1 diabetes, with at least one SNP in C3 significantly associated with clinically diagnosed type 1 diabetes.

引用

页数：10

共 42 条

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