IFIH1 polymorphisms are significantly associated with type 1 diabetes and IFIH1 gene expression in peripheral blood mononuclear cells

被引：126

作者：

Liu, Siyang ^{[1
]}

Wang, Hongjie ^{[1
]}

Jin, Yulan ^{[1
]}

Podolsky, Robert ^{[1
,2
]}

Reddy, M. V. Prasad Linga ^{[1
]}

Pedersen, Jennifer ^{[1
,2
]}

Bode, Bruce ^{[5
]}

Reed, John ^{[6
]}

Steed, Dennis ^{[6
]}

Anderson, Steve ^{[7
]}

Yang, Ping ^{[1
]}

Muir, Andy ^{[1
,3
]}

Steed, Leigh ^{[1
]}

Hopkins, Diane ^{[1
]}

Huang, Yihua ^{[1
,4
]}

Purohit, Sharad ^{[1
]}

Wang, Cong-Yi ^{[1
,4
]}

Steck, Andrea K. ^{[8
]}

Montemari, Annalisa ^{[1
]}

Eisenbarth, George ^{[8
]}

Rewers, Marian ^{[8
]}

She, Jin-Xiong ^{[1
,4
]}

机构：

[1] Med Coll Georgia, Ctr Biotechnol & Genom Med, Augusta, GA 30912 USA

[2] Med Coll Georgia, Dept Med, Augusta, GA 30912 USA

[3] Med Coll Georgia, Dept Pediat, Augusta, GA 30912 USA

[4] Med Coll Georgia, Dept Pathol, Augusta, GA 30912 USA

[5] Atlanta Diabet Associates, Atlanta, GA USA

[6] Southeast Endocrine Clin, Atlanta, GA USA

[7] Pediat Diabet, Atlanta, GA USA

[8] Univ Colorado, Hlth Sci Ctr, Barbara Davis Ctr Childhood Diabet, Aurora, CO 80045 USA

来源：

HUMAN MOLECULAR GENETICS | 2009年 / 18卷 / 02期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; LYMPHOID TYROSINE PHOSPHATASE; RHEUMATOID-ARTHRITIS; A946T POLYMORPHISM; GRAVES-DISEASE; LOCUS; PTPN22; SUSCEPTIBILITY; VARIANT; RISK;

D O I：

10.1093/hmg/ddn342

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Genome-wide association (GWA) studies revealed a number of single nucleotide polymorphisms (SNPs) significantly associated with type 1 diabetes (T1D). In an attempt to confirm some of these candidate associations, we genotyped 2046 Caucasian patients and 2417 normal controls from the United States for SNPs in five genomic regions. While no evidence was obtained for four genomic regions (rs2929366/NM_144715 on chromosome 3, rs9127/Q7Z4C4 on chromosome 5, rs1445898/CAPSL on chromosome 5 and rs2302188/NM_033543 on chromosome 19), we provide strong evidence for association between T1D and multiple SNPs in the IFIH1 linkage disequilibrium (LD) block on chromosome 2q. Among the 10 SNPs genotyped for the 2q region, four SNPs located within the IFIH1 gene or at the 5' region of IFIH1 showed significant association with T1D in the Georgia population [odds ratio (OR) = 1.7-1.9] with the best P-value found at SNP rs1990760 (P = 8 x 10(-8) and OR = 1.9). Several SNPs outside of the IFIH1 gene also showed significant but weaker associations. Furthermore, IFIH1 gene expression levels in peripheral blood mononuclear cells are significantly correlated with IFIH1 genotypes, and higher IFIH1 levels are found in individuals with the susceptible genotypes (P = 0.005). Thus, both genetic association and gene expression data suggest that IFIH1 is the most plausible candidate gene implicated in T1D in this LD block.

引用

页码：358 / 365

页数：8

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