Association of an Anti-inflammatory Cytokine Gene IL4 Polymorphism with the Risk of Type 2 Diabetes Mellitus in Korean Populations.
- Author:
Min Jin GO
1
;
Haesook MIN
;
Jong Young LEE
;
Sung Soo KIM
;
Yeonjung KIM
Author Information
1. Center for Genome Science, Korea National Institute of Health, Korea Centers for Disease Control and Prevention, Osong Health Technology Administration Complex, 187, Osongsaengmyeong2-ro, Gangoe-myeon, Cheongwon-gun, Chungcheongbuk-do, 363-951, Korea. kim
- Publication Type:Original Article ; Meta-Analysis
- Keywords:
type 2 diabetes mellitus;
single nucleotide polymorphisms;
IL4;
IL4R;
anti-inflammatory cytokine;
gene-gene interaction
- MeSH:
Alleles;
Case-Control Studies;
Cohort Studies;
Cytokines;
Diabetes Mellitus, Type 2;
Gene Expression;
Genes, Reporter;
Inflammation;
Insulin Resistance;
Interleukin-4;
Logistic Models;
Polymorphism, Single Nucleotide
- From:Genomics & Informatics
2011;9(3):114-120
- CountryRepublic of Korea
- Language:English
-
Abstract:
Chronic inflammation has been implicated as one of the important etiological factors in insulin resistance and type 2 diabetes mellitus (T2DM). To investigate the role of anti-inflammatory cytokines in the development of T2DM, we conducted a case-control study to assess the association between IL4/IL4R polymorphisms and disease risk. We firstly identified single nucleotide polymorphisms (SNP) at IL4 and IL4RA loci by sequencing the loci in Korean participants. Case-control studies were conducted by genotyping the SNPs in 474 T2DM cases and 470 non-diabetic controls recruited from community-based cohorts. Replication of the associated signals was performed in 1,216 cases and 1,352 controls. We assessed effect of IL4-IL4RA interaction on T2DM using logistic regression method. The functional relevance of the SNP associated with disease risk was determined using a reporter expression assay. We identified a strong association between the IL4 promoter variant rs2243250 and T2DM risk (OR=0.77; 95% CI, 0.67~0.88; p=1.65x10-4 in the meta-analysis). The reporter gene expression assay demonstrated that the presence of rs2243250 might affect the gene expression level with ~1.5-fold allele difference. Our findings contribute to the identification of IL4 as a T2D susceptibility locus, further supporting the role of anti-inflammatory cytokines in T2DM disease development.
