Vitamin D receptor polymorphisms: no association with type 1 diabetes in the Finnish population

Abstract

Objective: The effect of polymorphisms of the vitamin D receptor (VDR) gene on susceptibility to type 1 diabetes has recently been investigated extensively. Several findings on positive disease associations have been observed and, in addition, a protective effect of vitamin D supplementation has been reported. Design: We studied the effect of three vitamin D receptor gene polymorphisms (VDRA, VDRB, VDRF) on susceptibility to type 1 diabetes in a large case-control series (more than 2000 controls and about 1000 patients) from the Finnish population. Methods: A combination of case-control and affected-family based approaches was used. Subjects were genotyped for VDRA (ApaI), VDRB (BsmI) and VDRF (FokI) single nucleotide polymorphisms using a minisequencing reaction. Results: A few borderline significant associations were observed with both approaches used. In the case-control association analyses we found significant differences between cases and controls in frequencies of VDRB (P ¼ 0.024, all subjects and P ¼ 0.016, HLA DQB1 * 0302-positive subjects) and VDRF (P ¼ 0.0063, Turku cohort). In the total family set a decreased (39.3%) transmission of the VDRA-VDRB-VDRF haplotype 1-1-2 and an increased (60.3%) transmission of haplotype 2-1-2 to sons was seen (P ¼ 0.0059 and P ¼ 0.024 respectively). Transmission of the haplotype 2-2-1 to daughters was decreased (37.6%, P ¼ 0.022). Interestingly, we also observed significant differences in allele frequencies of the polymorphisms studied between populations from three different regions in Finland. Conclusions: All these differences disappeared after correction for multiple testing. We conclude that the single nucleotide polymorphisms analysed are unlikely to be associated with type 1 diabetes in the Finnish population.

Polymorphisms in the Vitamin D Receptor Gene and Parathyroid Hormone Gene in the Development and Progression of Diabetes Mellitus and its Chronic Complications, Diabetic Nephropathy and Non-Diabetic Renal Disease

“…It should be noted that some studies suggest weak associations of corresponding single nucleotide polymorphisms in VDR alleles or haplotypes with type 1 and type 2 DM [28,29]. However, while their haplotypes were reported as associated with type 1 diabetes in the German and Taiwan [30,31] population, recent data from a broad familial study did not prove such association in populations from UK, Finland, Norway and Romania statistically significant [32,33].…”

Vitamin D receptor gene polymorphisms in type 1 diabetes mellitus: a new pattern from Khorasan province, Islamic Republic of Iran

“…In Barcelona, Spain, the frequencies of bb, and especially combined bb/FF genotypes, were higher in type 1 DM patients than in controls [21]. However, in a Finnish population VDR polymorphisms had no association with type 1 DM [24], and a study in Santiago on children with type 1 DM demonstrated that the frequency of the b allele and bb genotype was significantly lower compared with the control group [22]. Surprisingly, a meta-analysis in 2006 also showed that there was no association between VDR gene polymorphisms and type 1 DM risk in case-control and family transmission studies [25].…”

Vitamin D receptor polymorphism and susceptibility to type 1 diabetes in chilean subjects: A case-parent study

“…The meaning of this observation remains unclear and its relevance must be checked the allele and haplotype distribution in different population samples [6][7][8]. Inconsistent gene-disease results previously reported in association studies [6][7][8] have encouraged us to check the relevance of VDR polymorphisms in different populations. Therefore, We have investigated three polymorphic sites of VDR gene on chromosome 12q12-14 as candidate for type 1 diabetes susceptibility locus for the first time in Chilean population.…”

“…Among them, polymorphic Bsm1 and Apa1 sites are present in intron 8, and a silent T to C substitution creates a Taq1 restriction site in exon 9 [5]. The meaning of this observation remains unclear and its relevance must be checked the allele and haplotype distribution in different population samples [6][7][8]. Inconsistent gene-disease results previously reported in association studies [6][7][8] have encouraged us to check the relevance of VDR polymorphisms in different populations.…”