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 χ 2 < 0.01). However, its insertion or deletion did not modulate the risk conferred by HLA- DQ8 ( DQA1*0301-DQB1*0302) (P χ 2 = 0.27) or - DQ2 ( DQA1*0501-DQB1*0201) (P χ 2 = 0.46). Thus, the HERV-K(C4) insertion is not associated with type I diabetes in Germans.