Abstract
The trigeminal autonomic cephalalgia, cluster headache (CH), is one of the most painful disorders known to man. One of the disorder’s most striking features is the reported diurnal rhythmicity of the attacks. For a majority of patients, the headache attacks occur at approximately the same time every day. Genetic variants of genes involved in the circadian rhythm such as Period Circadian Regulator 1, 2, and 3 (PER1, 2 and 3) are hypothesized to have an effect on the rhythmicity of the attacks. Six PER1, 2 and 3 genetic markers; the indel rs57875989 and five single nucleotide polymorphisms (SNPs), rs2735611, rs2304672, rs934945, rs10462020, and rs228697, were genotyped, using TaqMan® or regular polymerase chain reaction (PCR), in a Swedish CH case control material. Logistic regression showed no association between CH and any of the six genetic variants; rs57875989, p = 0.523; rs2735611, p = 0.416; rs2304672, p = 0.732; rs934945, p = 0.907; rs10462020, p = 0.726; and rs228697, p = 0.717. Furthermore, no difference in allele frequency was found for patients reporting diurnal rhythmicity of attacks, nor were any of the variants linked to diurnal preference. The results of this study indicate no involvement of these PER genetic variants in CH or diurnal phenotype in Sweden.
Highlights
Patients diagnosed with the neurological disorder cluster headache (CH) suffer from extremely painful headache attacks occurring once every other day up to eight times per day during an active cluster period [1]
A call rate of 99.50% was achieved for rs2735611, 99.92% for rs2304672, 98.42% for rs934945, 97.8% for rs10462020, and 98.2% for rs228697. rs934945, rs57875989, rs2304672, rs10462020, and rs228697 were in accordance with Hardy-Weinberg equilibrium (HWE) (p > 0.05), data available upon request
In order to account for the higher percentage of males in the patient cohort compared to controls (65.8% vs. 56.8%), we analyzed the data using a logistic regression under an additive model with sex as a covariate
Summary
Patients diagnosed with the neurological disorder cluster headache (CH) suffer from extremely painful headache attacks occurring once every other day up to eight times per day during an active cluster period [1]. Autonomic symptoms, such as lacrimation and swelling around the eye, accompany the attacks [1]. CLOCK/BMAL1 transcribe their own inhibitors, Period Circadian Regulator 1, 2 and 3 (PER1/2/3) and Cryptochrome 1/2 (CRY1/2) This produces a feedback loop which runs in approximately 24 h cycles and allows for the variation of expression of circadian-regulated genes throughout the day [3]. Along with this robust core genetic feedback loop, environmental cues and other circadian related genes form the complex network which dictates our diurnal rhythm
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