Investigating Vitamin D Receptor Genetic Markers in a Cluster Headache Meta-Analysis

Abstract

Patients diagnosed with the primary headache disorder known as cluster headache (CH) commonly report that their headache attacks occur in patterns of both circadian and seasonal rhythmicity. Vitamin D is essential for a variety of bodily functions and vitamin D levels are largely regulated by daylight exposure in connection with seasonal variation. For this Sweden-based study, the association between CH and three single-nucleotide polymorphisms in the vitamin D receptor gene, rs2228570, rs1544410, and rs731236, were investigated, as well as CH bouts and trigger factors in relation to seasonal and weather changes. Over 600 study participants with CH and 600 controls were genotyped for rs2228570, and genotyping results for rs1544410 and rs731236 were obtained from a previous genome-wide association study. The genotyping results were combined in a meta-analysis, with data from a Greek study. No significant association was found between rs2228570 and CH or the CH subtype in Sweden, nor did the meta-analysis show significant results for any of the three markers. The most common period of the year to experience CH bouts in Sweden was autumn, and conditions linked to weather or weather changes were also identified as potential triggers for CH bouts for a quarter of the responders who reported bout triggers. Though we cannot rule out vitamin D involvement in CH, this study does not indicate any connection between CH and the three vitamin D receptor gene markers.

Keywords: BsmI; Fok1; Taq1; pain; rs1544410; rs2228570; rs731236; seasonal rhythmicity.

Figure 1

Patterns of seasonal rhythmicity for CH bouts, showing CH individuals who answered questions on seasonal rhythmicity in regard to their CH bouts (total—n = 301; those who answered yes—n = 149 (49.5%)). Percentages are based on CH individuals who experienced seasonal rhythmicity. CH = cluster headache. Patients were allowed to check more than one alternative.