title: The variable endogenous retroviral insertion in the human complement C4 gene: a transmission study in type I diabetes mellitus.
abstract: A variable endogenous retroviral element has been identified in intron 9 of the complement C4 gene [HERV-K(C4)], which maps to the class III region of the major histocompatibility complex (MHC) on chromosome 6p21.3. Genetic susceptibility to type I diabetes is mainly conferred by the MHC locus and the complement C4 region has been implied to contribute to human leukocyte antigen DQ (HLA-DQ) mediated disease risk. As the HERV-K(C4) insertion has been suggested to modulate expression of homologous genes, we investigated its transmission in 220 families with an offspring affected by type I diabetes as a potential disease susceptibility marker. There was no preferential transmission of the HERV-K(C4) insertion to affected offspring (P(TDT) = 0.79). Although 77.7% of HLA-DQ8 carried the HERV-K(C4) insertion, only 52.9% of -DQ2 haplotypes did (P(chi(2)) < 0.01). However, its insertion or deletion did not modulate the risk conferred by HLA-DQ8 (DQA1*0301-DQB1*0302) (P(chi(2)) = 0.27) or -DQ2 (DQA1*0501-DQB1*0201) (P(chi(2)) = 0.46). Thus, the HERV-K(C4) insertion is not associated with type I diabetes in Germans.
authors.affiliation: Department of Internal Medicine I, Division of Endocrinology, University Hospital, Frankfurt am Main, Germany.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pani
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Wood
authors.forename: Katrin
authors.initials: K
authors.lastname: Bieda
authors.forename: Ralf R
authors.initials: RR
authors.lastname: Toenjes
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Usadel
authors.forename: Klaus
authors.initials: K
authors.lastname: Badenhoop
mesh_terms: D003181:Complement C4 / Q000235:genetics*; D004251:DNA Transposable Elements; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D020077:Endogenous Retroviruses / Q000235:genetics*; D005786:Gene Expression Regulation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics; D006801:Humans
chemical_list: D003181:Complement C4; D004251:DNA Transposable Elements; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C109756:HLA-DQ8 antigen