Multifactor-dimensionality reduction shows a two-locus interaction associated with Type 2 diabetes mellitus

被引:165
作者
Cho, YM
Ritchie, MD
Moore, JH
Park, JY
Lee, KU
Shin, HD
Lee, HK
Park, KS
机构
[1] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 110744, South Korea
[2] Seoul Natl Univ Hosp, Clin Res Inst, Genome Res Ctr Diabet & Endocrine Dis, Seoul 110744, South Korea
[3] Vanderbilt Univ, Sch Med, Program Human Genet, Nashville, TN 37212 USA
[4] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA
[5] Univ Ulsan, Sch Med, Dept Internal Med, Seoul, South Korea
[6] SNP Genet, Dept Genet Epidemiol, Seoul, South Korea
关键词
multifactor-dimensionality reduction; Type 2 diabetes mellitus; gene to gene interaction; uncoupling protein 2; peroxisome proliferator-activated receptor gamma;
D O I
10.1007/s00125-003-1321-3
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aims/hypothesis. Type 2 diabetes mellitus is a complex genetic disease, which results from interactions between multiple genes and environmental factors without any single factor having strong independent effects. This study was done to identify gene to gene interactions which could be associated with the risk of Type 2 diabetes. Methods. We genotyped 23 different loci in the 15 candidate genes of Type 2 diabetes in 504 unrelated Type 2 diabetic patients and 133 non-diabetic control subjects. We analysed gene to gene interactions among 23 polymorphic loci using the multifactor-dimensionality reduction (MDR) method, which has been shown to be effective for detecting and characterising gene to gene interactions in case-control studies with relatively small samples. Results. The MDR analysis showed a significant gene to gene interaction between the Ala55Val polymorphism in the uncoupling protein 2 gene (UCP2) and the 161C>T polymorphism in the exon 6 of peroxisome proliferator-activated receptor gamma (PPARgamma) gene. This interaction showed the maximum consistency and minimum prediction error among all gene to gene interaction models evaluated. Moreover, the combination of the UCP2 55 Ala/Val heterozygote and the PPARgamma 161 C/C homozygote was associated with a reduced risk of Type 2 diabetes (odds ratio: 0.51, 95% CI: 0.34 to 0.77, p=0.0016). Conclusions/interpretation. Using the MDR method, we showed a two-locus interaction between the UCP2 and PPARgamma genes among 23 loci in the candidate genes of Type 2 diabetes. The determination of such genotype combinations contributing to Type 2 diabetes mellitus could provide a new tool for identifying high-risk individuals.
引用
收藏
页码:549 / 554
页数:6
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