title: High prevalence of HHV8 infection and specific killer cell immunoglobulin-like receptors allotypes in Sardinian patients with type 2 diabetes mellitus.
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 virus-disease 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 HLA-C1C1 genotype in the type 2 diabetes patients infected with HHV8 compared to uninfected ones (62% vs. 15%, P < 0.0001, OR = 8.64). 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 contributing to the development of type 2 diabetes.
authors.affiliation: Department of Medical Sciences, Microbiology Unit, University of Ferrara, Ferrara, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Caselli
authors.forename: Roberta
authors.initials: R
authors.lastname: Rizzo
authors.forename: Angela
authors.initials: A
authors.lastname: Ingianni
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Contini
authors.forename: Raffaello
authors.initials: R
authors.lastname: Pompei
authors.forename: Dario
authors.initials: D
authors.lastname: Di Luca
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000821:virology*; D004198:Disease Susceptibility; D005260:Female; D005787:Gene Frequency; D006566:Herpesviridae Infections / Q000453:epidemiology* / Q000821:virology; D019288:Herpesvirus 8, Human / Q000302:isolation & purification*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D015995:Prevalence; D054340:Receptors, KIR / Q000235:genetics*; D055815:Young Adult
chemical_list: D054340:Receptors, KIR
keywords: HHV8; KIR genotype; type 2 diabetes