NASHVILLE—Single-nucleotide polymorphisms (SNPs) in the CYP2J2 region of chromosome 1 may be associated with an increased risk of multiple sclerosis (MS) and higher levels of prolactin, according to research presented at the 2018 CMSC Annual Meeting. “To our knowledge, this is the first report to show an association between genetic variants within this region and either MS status or the level of serum prolactin,” said Samantha Jack, Research Coordinator at Saunders Medical Center in Wahoo, Nebraska, and colleagues.
Although the cause of MS is unknown, a combination of genetic, environmental, and infectious risk factors may contribute to its pathogenesis, said Ms. Jack and colleagues. Vitamin D has been suggested as the most attractive environmental factor. In addition, the CYP2J2 gene has been identified as having a role in serum vitamin D levels in cattle, and the CYP2J2-containing region on bovine chromosome 3 is syntenic with that on human chromosome 1, the researchers said.
Evaluating SNPs in the CYP2J2 Region
Ms. Jack and colleagues conducted a study to determine whether associations exist between variations in the genomic region of CYP2J2 and MS 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.
Participants were recruited from Nebraska, Iowa, and Kansas between October 2014 and December 2016 to participate in a single blood draw.
Ms. Jack and colleagues collected blood samples from 220 patients with MS and 238 age- and sex-matched controls. DNA from blood samples was genotyped for 94 SNPs in a 255,348 base-pair region of chromosome 1 that included CYP2J2 and C1orf87. Researchers analyzed serum samples to quantify concentrations of vitamin D, vitamin D–binding protein, alkaline phosphatase, and prolactin. Almost all participants with MS took supplemental vitamin D.
The 458 participants in the study were predominately Caucasian and had an average age of about 50, said Ms. Jack.
SNPs in the CYP2J2 region were associated with an increased risk of MS. These associations were not significant following Bonferroni correction. Several other SNPs in the CYP2J2 region were associated with prolactin levels, but the associations were not significant following the Bonferroni correction. No SNPs in this region showed significant associations between levels of vitamin D, vitamin D–binding protein, calcium, or alkaline phosphatase, but vitamin D levels may have been skewed since many patients with MS were taking vitamin D supplements, said the researchers.
Overall, SNPs downstream of CYP2J2 in the C1orf87 gene were associated with prolactin levels, and SNPs in the intergenic region between CYP212 and C1orf87 may be associated with MS, said the researchers.
Study Limitations and Future Directions
Study limitations include that the study population was homogeneous (ie, middle-aged and white from the Midwest) and that samples were not always taken in the morning after fasting, which may have affected prolactin levels, said Ms. Jack.
“We are in the process of undertaking a genome-wide association study to continue this work,” Ms. Jack said. “We are currently enrolling more subjects to have a well-powered study, and we hope to have a small subset of people who have not taken vitamin D supplementation so that we will be able to analyze those values.”
—Erica Tricarico