Different factors may be involved in the clinical heterogeneity of spinal muscular atrophy disease. The vitamin D receptor (VDR) might be a candidate gene for this disease. Our study aimed to assess the preferential transmission of VDR polymorphisms from parents to SMA children. We genotyped 261 subjects (87 SMA nuclear families) for VDR FokI, BsmI, ApaI, and TaqI polymorphisms. The transmission of the genetic marker was estimated with Plink and FBAT software. It detected a preferential transmission of the rs731236 and rs7975232 variants to SMA1 patients and of rs1544410 variants to SMA2 patients. The variants of rs2228570 were preferentially transmitted to parents of all SMA patients. Haplotype analysis identified that haplotypes C-C-G-A and T-A-A-G seem to be involved in the booth type of SMA whereas the impact of T-A-A-A seems to be limited only to SMA2. Strong linkage disequilibrium (LD) between rs7975232 and rs1544410 was detected in samples from parents. Even though we investigated a small number of nuclear families the results suggest a potential link between VDR polymorphisms and SMA disease.
Vitamin D receptor gene polymorphisms have been intensively studied in relation with many diseases, including neurodegenerative disorders. We investigated the relationship between VDR polymorphisms and spinal muscular atrophy type I, a common lower motor neuron disease. Forty clinically and molecular diagnosed patients and 54 healthy subjects were analyzed PCR-RFLP method. We found an association trend (p=0.01) for the BsmI polymorphism taken individually and a significant association for two of four-locus inferred haplotypes (fBAt and fbaT). Also, baT, Bat and bAT were the most frequent estimated haplotypes in our control group, which is in accordance with previous published reports for Caucasian populations. We concluded that future studies performed in order to identify possible modifier genes for spinal muscular atrophy disease should take into consideration the involvement of vitamin D receptor gene polymorphisms.
