title: Prevalence of vitamin D receptor gene polymorphisms FokI and BsmI in Brazilian individuals with type 1 diabetes and their relation to beta-cell autoimmunity and to remaining beta-cell function.
abstract: The effect of the vitamin D receptor (VDR) gene polymorphisms on susceptibility to type 1 diabetes (T1DM) is heterogeneous. Genetic factors may also influence the residual beta-cell function. We studied the frequency of VDR FokI (rs10735810) and BsmI (rs154410) polymorphisms in T1DM and their relationship to beta-cell autoimmunity and residual beta-cell function. We genotyped 189 T1DM (diabetes duration, 7.1 +/- 5.4 years) and 194 controls (C) by restriction length polymorphism-polymerase chain reaction. GAD65Ab, IA2Ab, ionized calcium (iCa), HbA(1c)and fasting C-peptide (FCP) were evaluated. FCP values greater than 0.6 ng/ml were considered as residual beta-cell function. The BsmI was more frequent in the C (bb plus Bb 79.1 C vs. 66.1% T1DM, p = 0.006), and the FokI polymorphism frequencies were similar between T1DM and C. We did not observe differences in pancreatic autoantibody profiles according to VDR genotypes. We observed that T1DM with f allele tended to have lower residual pancreatic beta-cell function (5.8% ff and Ff vs. 14.3% FF, p = 0.074) with similar age, diabetes duration, AAb positivity, HbA(1c), and iCa. Age at diagnosis of T1DM with BsmI polymorphism tended to be greater (10.7 +/- 4.9 bb and Bb vs. 9.3 +/- 4.5 years BB, p = 0.06). In conclusion, the results of this study showed no relationship between VDR polymorphisms and beta-cell autoimmunity; however we observed a relationship with age and remaining beta-cell function in Brazilian individuals with T1DM. These data may contribute to understanding the heterogeneous relationship between genetic markers and clinical features observed in this disease.
authors.affiliation: Department of Endocrinology, São Paulo Federal University (UNIFESP), São Paulo, Brazil.
authors.forename: Denise B
authors.initials: DB
authors.lastname: Mory
authors.forename: Eloá R
authors.initials: ER
authors.lastname: Rocco
authors.forename: Walkíria L
authors.initials: WL
authors.lastname: Miranda
authors.forename: Teresa
authors.initials: T
authors.lastname: Kasamatsu
authors.forename: Felipe
authors.initials: F
authors.lastname: Crispim
authors.forename: Sérgio A
authors.initials: SA
authors.lastname: Dib
mesh_terms: D000293:Adolescent; D015551:Autoimmunity; D001938:Brazil; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics*; D055815:Young Adult
chemical_list: D018167:Receptors, Calcitriol