Epistatic effects of genes encoding tumor necrosis factor-alpha, immunoglobulin allotypes, and HLA antigens on susceptibility to non-insulin-dependent (type 2) diabetes mellitus.
Non-insulin-dependent diabetes mellitus (NIDDM) is a complex disease with a very high degree of heritability. Linkage and segregation analyses have not been very productive in identifying genes responsible for polygenic diseases such as NIDDM, and the majority of the genes determining susceptibility to this disorder remain to be identified. Using a case-control study design, we investigated the possible roles of genes coding for HLA class II antigens, tumor necrosis factor-alpha (TNF-alpha), and immunoglobulin (Ig) allotypes (GM and KM) in a group of Caucasians from Belgium (214 NIDDM patients and 200 controls). All genetic markers were determined by polymerase chain reaction-based methods. We demonstrate that particular homozygous genotypes of TNF-alpha and GM and KM allotypes epistatically interact with HLA-DQalpha1(Arg 52) and contribute to an increased relative risk of NIDDM.
Pandey
J P
JP
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425-2230, USA.
Zamani
M
M
Cassiman
J J
JJ
D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000276:immunology*; D005787:Gene Frequency; D005802:Genes, MHC Class II; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007126:Immunoglobulin Allotypes / Q000235:genetics*; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D006680:HLA Antigens; D007126:Immunoglobulin Allotypes; D014409:Tumor Necrosis Factor-alpha