Gender-specific association of vitamin D receptor polymorphism combinations with type 1 diabetes mellitus

• Published in: European journal of endocrinology Vol. 147; no. 6; pp. 803 - 808
• Main Authors: Gyorffy, B, Vasarhelyi, B, Krikovszky, D, Madacsy, L, Tordai, A, Tulassay, T, Szabo, A
• Format: Journal Article
• Language: English
• Published: Colchester European Society of Endocrinology 01.12.2002; Portland Press
• Subjects: Adolescent; Alleles; Biological and medical sciences; Child; Child, Preschool; Control Groups; Diabetes Mellitus, Type 1 - genetics; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Gene Frequency; Genetic Predisposition to Disease - genetics; Humans; Infant; Male; Medical sciences; Polymorphism, Genetic; Receptors, Calcitriol - genetics; Sex Characteristics; Endocrinopathy; Human; Immunopathology; Prevalence; Sex; Autoimmune disease; Infant; Allele; Association; Gene; Vitamin D; Adolescent; Risk factor; Insulin dependent diabetes; Molecular epidemiology; Child; Comparative study; Polymorphism; Biological receptor
• ISSN: 0804-4643; 1479-683X
• DOI: 10.1530/eje.0.1470803

OBJECTIVE: Recent data have indicated the significance of vitamin D receptor (VDR) polymorphisms in type 1 diabetes mellitus (T1DM). We have studied the association of five known restriction enzyme polymorphisms of the VDR gene in patients with T1DM. DESIGN AND METHODS: One hundred and seven children with T1DM (T1DM for 5 Years; age, 1-14 Years; boys/girls, 57/50; body mass index, 17.0+/-2.3 kg/m(2); haemoglobin A(Ic) (HbA(Ic)), 7.87+/-1.05) and 103 healthy subjects were enrolled. The VDR polymorphisms ApaI, BsmI, FokI, TaqI and Tru9I ("a", "b", "f", "t" and "u" alleles respectively) were investigated. RESULTS: The "t" and "T" alleles miss the Hardy-Weinberg equilibrium (P<0.01) in control and diabetic populations; we therefore excluded this polymorphism from further analysis. We did not find a difference in the allele prevalence in T1DM patients and controls of any of the five polymorphisms. However, when the "b", "a" and "u" alleles were simultaneously compared in girls, there was a significantly higher prevalence in patients with diabetes compared with controls ("b"+"a"+"u" present/absent: healthy, 0/53; diabetic, 13/37; P<0.005). In boys the prevalence of "b"+"a"+"u" genotype was similar in T1DM and controls. CONCLUSIONS: The impact of the "t" allele cannot be investigated in this study population. Not a single VDR polymorphism increases the susceptibility to T1DM. The common presence of the "b", "a" and "u" alleles greatly increases the probability of T1DM in girls.