Michael A. Pani

CYP27B1 polymorphisms variants are associated with type 1 diabetes mellitus in Germans.

CYP27B1 (25-hydroxyvitamin D(3)-1alpha-hydroxylase) catalyzes the metabolization of 25-hydroxyvitamin D(3) to 1,25(OH)(2)D(3) the most active natural Vitamin D metabolite. 1,25(OH)(2)D(3) plays a role in the regulation of autoimmunity and cell proliferation and prevents the development of autoimmune diabetes mellitus in animal models besides other autoimmune disorders. One hundred and eighty-seven families with one offspring affected with type1diabetes mellitus were genotyped for the polymorphisms in the promoter region (-1260 C/A) and intron 6 (2338 T/C) of the CYP27B1 gene on chromosome 12 q13.1-13.3 and extended transmission disequilibrium tests (ETDT) were performed. The haplotype CT (-1260 A/2338 T) was significantly more often transmitted to affected offspring (96 transmitted (T) versus 63 not transmitted (NT), P = 0.0089). While the AT (-1260 C/2838 T) was significantly less often transmitted (37 T versus 60 NT, P = 0.0195). This study suggests that CYP27B1 haplotypes may confer susceptibility to type 1 diabetes mellitus in Germans.

Preliminary evidence that an endogenous retroviral long‐terminal repeat (LTR13) at the HLA‐DQB1 gene locus confers susceptibility to Addison's disease

OBJECTIVE Addisons disease is associated with particular haplotypes of the human leucocyte antigen (HLA) region [DQA1*0501‐DQB1*0201 (DQ2) and DQA1*0301‐DQB1*0302 (DQ8)]. This locus harbours several human endogenous retroviral (HERV) long‐terminal repeats (LTR). LTRs within the HLA region have been shown to confer additional susceptibility to type 1 diabetes and rheumatoid arthritis.

The variable endogenous retroviral insertion in the human complement C4 gene: a transmission study in type I diabetes mellitus ☆

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.

Digging the Genome for Diabetes Mellitus: The 2nd ADA Research Symposium on the Genetics of Diabetes, San Jose, CA, USA, 17–19 October 1999

The diabetes genetics community recently met in California to discuss the impact that the latest findings in susceptibility mapping might have on our understanding of the pathophysiology of diabetes mellitus and its long-term complications. Organized by Ralph DeFronzo (San Antonio, TX) and Alan Permutt (St Louis, MO) the symposium covered the genetics of type 1 and type 2 diabetes, obesity, approaches to population selection and stratification, quantitative trait analysis, epidemiological tools and technological advances in genotyping.