Variations within a 255,348 Base-Pair Region of Chromosome 1 That Show Association with Serum Prolactin Levels or MS Status.

Background: Multiple sclerosis is a chronic, inflammatory and autoimmune disease of the central nervous system. MS has no cure and its cause remains unknown. The current belief is that a combination of genetic, environmental and infectious risk-factors contribute to the pathogenesis of MS. Vitamin D has been suggested as the most attractive environmental factor. The CYP2J2 gene was identified as having a role in serum vitamin D levels in cattle. The CYP2J2-containing region on bovine chromosome 3 is syntenic with that on human chromosome 1.

Objectives: To determine if associations exist between variations in a genomic region within human chromosome 1 and multiple sclerosis status or levels of serum markers associated with vitamin D and calcium metabolism such as prolactin, vitamin D, vitamin-D binding protein, alkaline phosphatase, and calcium.

Methods: MS patients and unaffected age and sex-matched control subjects who gave informed consent participated in a single blood draw. DNA, from blood samples, was genotyped for 94 SNPs in a 255,348 base-pair region of chromosome 1 that included CYP2J2 and c1orf87. Serum samples were analyzed to quantify concentrations of vitamin D, vitamin D binding protein, calcium, alkaline phosphatase and prolactin. Nearly all MS subjects in the study took supplemental vitamin D.

Results: We report characteristics of MS patients (n=220) and controls (n=238) as well as the results of serum concentrations and genetic testing. SNPs in the CYP2J2 region are associated with an increased risk of MS (rs111695923, P=0.008294; rs1315673, P=0.02548; both not significant following Bonferroni correction) and higher levels of prolactin (rs675493, P=0.0000902; rs602488, P=0.0002931; both significant following Bonferroni correction) There were also several other SNPs in the same region associated with prolactin levels that were not significant following Bonferroni correction but were all p < 0.009. No SNPs in this region showed associations that were significant following Bonferroni correction with levels of vitamin D, vitamin D binding protein, calcium or alkaline phosphatase. However, vitamin D levels may have been skewed due to supplementation of MS patients with vitamin D.

Conclusions: This study presents evidence that suggests an association between different SNPs in the CYP2J2 region and prolactin levels or MS.  Specifically, SNPs downstream of CYP2J2 in the C1orf87 gene are associated with prolactin levels and SNPs in the intergenic region between CYP2J2 and C1orf87 may be associated with MS.  To our knowledge, this is the first report to show association between genetic variants within this region and either MS status or the level of serum prolactin.