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


METHODS
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=0.024, all subjects and P=0.016, HLA DQB1*0302-positive subjects) and VDRF (P=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=0.0059 and P=0.024 respectively). Transmission of the haplotype 2-2-1 to daughters was decreased (37.6%, P=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.
Turpeinen
Hannu
H
JDRF Centre for Prevention of Type 1 Diabetes in Finland and Department of Virology, University of Turku, Turku, Finland. hannu.turpeinen@utu.fi
Hermann
Robert
R
Vaara
Satu
S
Laine
Antti-Pekka
AP
Simell
Olli
O
Knip
Mikael
M
Veijola
Riitta
R
Ilonen
Jorma
J
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005387:Finland / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics*
D018167:Receptors, Calcitriol