Multiple sclerosis (MS) is the most frequent nontraumatic disabling neurological disease among young adults. Previous studies have examined the association of rs703842 in CYP27B1 with MS susceptibility, with inconsistent results reported.
The objective of this study is to conduct a systematic literature search and perform meta-analyses to examine whether rs703842 is associated with MS risk.
We searched potential literature in PubMed, Cochrane Library, Embase, Google Scholar, Web of Science, and HuGE by using the following inclusion criteria: studies were on human subjects; the studies were case–control studies; studies included subjects who had MS and those who did not have MS; and the studies provided genotype data for rs703842 for subjects who had and did not have MS, or provided odds ratios (ORs) and the 95% confidence intervals (CIs) for assessing the association of rs703842 with MS, or provided sufficient data for the calculation of OR and the 95% CI. We used random-effects models to calculate the OR as a measure of association. We used I2 to assess between-study heterogeneity, and a funnel plot and Egger test to assess publication bias.
Seven studies published since 2008 met the eligibility criteria and were included in the meta-analyses. We found that the C allele was significantly associated with reduced MS susceptibility (OR = 0.88, 95% CI: 0.80–0.89; P < 0.0001). We also found significant association of rs703842 with MS risk using a dominant and a recessive model (both P < 0.0002). Our results remain unchanged if our meta-analysis was limited to studies that included only Caucasian participants (OR = 0.85, 95% CI: 0.80–0.90; P < 0.0001).
Our study has several limitations: The sample size is limited; We were unable to control for some important confounding factors as data for individual participant were not available; and Most of the included studies focus on MS risk in Caucasian. As a result, we could not perform meta-analysis for assessing the relationship in other ethnic groups.
In summary, we found that the genetic variant rs703842 in CYP27B1 is associated with MS risk in Caucasians. More studies with larger sample size that control for important confounding factors are needed to validate the findings from this study.