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Vitamin D receptor initiation codon polymorphism influences genetic susceptibility to type 1 diabetes mellitus in the Japanese population

DOI: 10.1186/1471-2350-2-7

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We found a significantly higher prevalence of the F allele / the FF genotype in the patients compared to the controls (P = 0.0069 and P = 0.014, respectively). Genotype and allele frequencies differed significantly between GAD65-Ab-positive patients and controls (P = 0.017 and P = 0.012, respectively), but neither between GAD65-Ab-negative patients and controls (P = 0.68 and P = 0.66, respectively) nor between GAD65-Ab-positive and -negative patients (P = 0.19 and P = 0.16, respectively).Our findings suggest that the vitamin D receptor initiation codon polymorphism influences genetic susceptibility to T1DM among the Japanese. This polymorphism is also associated with GAD65-Ab-positive T1DM, although the absence of a significant difference between GAD65-Ab-negative patients and controls might be simply due to the small sample size of patients tested for GAD65 antibodies.Type 1 diabetes mellitus (T1DM) is a multifactorial disease with a strong genetic component [1]. The main genetic contribution to T1DM susceptibility lies in the major histocompatibility complex (MHC) on the short arm of chromosome 6; several non-MHC chromosomal regions are also involved [2]. Several approaches have been used to identify T1DM susceptibility regions, including case-control studies of candidate genes [human leukocyte antigen (HLA), insulin gene regulatory region, interleukin-1 receptor type 1 (ILIR1)] [3,4,5,6], combined linkage and association-based studies of candidate genes [cytotoxic T lymphocyte associated-4 (CTLA-4)] [7], and systematic total genome searches in addition to analyses of individual chromosomal regions [8,9,10,11,12,13,14,15,16].There are clear differences in immunogenetic predisposition to T1DM between countries, and disease incidence seems to vary along with these differences in predisposition [1]. The incidence of T1DM in Southern India (10.4/100000 cases per year) is similar to that in Asian children in the UK and Caucasian children of European extraction [17,18].


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