Background and objective: In order to assess whether vitamin D receptor gene polymorphisms are involved in the genetic regulation of type 1 diabetes susceptibility, a case-control study was conducted in two Spanish populations with different genetic backgrounds.
Patients and method: 155 patients with childhood-onset type 1 diabetes and 280 healthy controls from Barcelona, and 89 patients and 116 controls from Navarre were studied for vitamin D receptor gene polymorphisms in peripheral blood DNA. Intron 8 (BsmI) and exon 2 (FokI) segments were amplified by PCR and sequenced to determine each corresponding genotype. Differences for allele, genotype and combined haplotype and genotype distribution between patients and controls within each population and between the two populations were analyzed.
Results: BsmI genotype and allele frequencies showed a tendency towards increased bb genotype and b allele frequencies in Barcelona patients and the tendency was inverse in Navarre. FokI polymorphism distribution analysis showed a significant decrease in ff genotype (p = 0.016) in patients versus controls from Navarre. Combined genotypes showed homozygous bb/FF genotype to be increased in Barcelona patients (p = 0.04) whereas homozygous bb/ff genotype was decreased in Navarre patients (p = 0.02) versus their corresponding controls. BF haplotype frequency distribution between patients and controls was inverse and significantly different between Barcelona and Navarre (p = 0.04).
Conclusions: Combined genotypes for vitamin D receptor gene polymorphisms at intron 8 and exon 2 suggest that the more active form of vitamin D receptor gene (FF genotype) can be increased in Mediterranean diabetic patients whereas the less active form (ff genotype) can be decreased in those from Navarre. Our results suggest that, in both groups, the F allele of exon 2 VDR gene polymorphism may increase type 1 diabetes susceptibility.