A combination of human leukocyte antigen DQB1*02 and the tumor necrosis factor alpha promoter G308A polymorphism predisposes to an insulin-deficient phenotype in patients with type 2 diabetes

The Journal of Clinical Endocrinology and Metabolism
Haiyan LiTiinamaija Tuomi

Abstract

Our previous results have suggested that genes outside the human leukocyte antigen (HLA) class II locus may affect the phenotype of type 2 diabetic patients from families with both type 1 and type 2 diabetes (mixed type 1/2). To study whether the TNF alpha gene could be such a modifying gene, we studied TNF alpha promoter polymorphisms (G-->A substitution at positions -308 and -238) in relation to HLA-DQB1 genotypes in type 2 patients from mixed type 1/2 families or common type 2 diabetes families as well as in patients with adult-onset type 1 diabetes and control subjects. The TNF alpha(308) AA/AG genotype frequency was increased in adult onset type 1 patients (55%, 69 of 126), but it was similar in type 2 patients from type 1/2 families (35%, 33/93) or common type 2 families (31%, 122 of 395), compared with controls (33%, 95/284; P < 0.0001 vs. type 1). The TNF alpha(308) A and DQB1*02 alleles were in linkage disequilibrium in type 1 patients (Ds = 0.81; P < 0.001 vs. Ds = 0.25 in controls) and type 2 patients from type 1/2 families (Ds = 0.59, P < 0.05 vs. controls) but not in common type 2 patients (Ds = 0.39). The polymorphism was associated with an insulin-deficient phenotype in the type 2 patients from type 1/2 families ...Continue Reading

Citations

May 18, 2012·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Gisela BarbisanCarlos Daniel Golijow
May 13, 2010·BMC Medical Genetics·Vesna BoraskaEleftheria Zeggini
Mar 24, 2007·Clinical Chemistry and Laboratory Medicine : CCLM·Constantina PapoutsakisGeorge V Dedoussis
May 10, 2013·American Journal of Reproductive Immunology : AJRI·Zofia Maria PiosikOle Bjarne Christiansen
May 30, 2009·Diabetes Research and Clinical Practice·Ren-Nan FengChang-Hao Sun
May 6, 2015·Osong Public Health and Research Perspectives·Hasan GolshaniSalar Bakhtiyari
May 6, 2020·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·Mengwei LiuWanyang Liu

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