High prevalence of HHV8 infection and specific killer cell immunoglobulin-like receptors allotypes in Sardinian patients with type 2 diabetes mellitus

Caselli E;Rizzo R;INGIANNI, ANGELA;Contini P;POMPEI, RAFFAELLO;Di Luca D.

2014-01-01

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Abstract

The development of type 2 diabetes is thought to involve both environmental, possibly infectious, and genetic factors. Recently, a high prevalence of human herpesvirus 8 (HHV8) infection was observed in type 2 diabetes patients, and specific killer cell immunoglobulin-like receptors (KIR) allotypes were associated to both increased susceptibility to herpesvirus infection and risk to develop diabetes. However, no clear gene-disease or virusdisease associations have been established. To investigate the possible interplay between HHV8 infection, KIR allotype and type 2 diabetes, virus prevalence and KIR genotype were analyzed by PCR in 168 patients affected by type 2 diabetes and 108 control individuals belonging to the Sardinian population. Results showed a significant increase of HHV8 prevalence in type 2 diabetes patients versus controls (57% vs. 17%, P <0.001), and a significant increase of KIR2DL2/DS2 homozygosity in diabetes patients infected with HHV8 compared to uninfected ones (64% vs. 14%, P <0.0001), resulting in a significant OR of 11.31. In addition, the analysis of the frequency of the KIR2DL2/DS2 receptor and its HLA-C1 ligand, accordingly to the status of HHV8 infection, showed a significant increased correlation between KIR2DL2/DS2, type 2 diabetes and HLAC1C1 genotype in the type 2 diabetes patients infected with HHV8 compared to uninfected ones (62% vs. 15%, P <0.0001, OR¼8.64). These findings provide preliminary evidence that HHV8 infection might be a cofactor for type 2 diabetes in a specific subset of genetically susceptible individuals, and suggest the possibility that such patients might have an impaired immune-mediated component 2013 WILEY PERIODICALS, INC. 3 Raffaello Pompei, contributing to the development of type 2 diabetes.