Investigation of vitamin D receptor polymorphisms in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) patients manifest aberrations in the vitamin D endocrine system, with a vitamin D deficiency. Genetic investigations have identified those proteins which link vitamin D to ALS pathology: major histocompatibility complex class II molecules, toll-like receptors, poly(ADP ribose) polymerase-1, haeme oxygenase-1, the reduced form of nicotinamide adenine dinucleotide phosphate and calcium-binding proteins. Vitamin D additionally impacts ALS through cell-signalling mechanisms: glutamate, matrix metalloproteinases, the Wnt/β-catenin signalling pathway, mitogen-activated protein kinase pathways, prostaglandins, reactive oxygen species and nitric oxide synthase, but its role has been only poorly investigated.

Our aim was to investigate vitamin D receptor (VDR) gene single nucleotide polymorphisms (SNPs) in an ALS population. This gene encodes the nuclear hormone receptor for vitamin D3.

A total of 75 consecutive sporadic ALS patients (~20% of the Hungarian ALS population) and 97 healthy controls were enrolled to investigate the possible effects of the different VDR alleles. A restriction fragment length polymorphism technique was utilized for allele discrimination.

One of the four investigated SNPs was associated with the disease, but none of the alleles of these SNPs influenced the age at disease onset. The ApaI A allele was more frequent in the ALS group than in the control group and may be an ALS risk factor.

This is the first verification of the genetic link between ALS and VDR. However, further studies are needed to confirm these findings.