Sutherland Heidi G, Champion Morgane, Plays Amelie, Stuart Shani, Haupt Larisa M, Frith Alison, MacGregor E Anne, Griffiths Lyn R
Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
Clinithink Limited, Bridgend, UK.
Gene. 2017 Apr 5;607:36-40. doi: 10.1016/j.gene.2017.01.008. Epub 2017 Jan 13.
Migraine is a common, disabling headache disorder, which is influenced by multiple genes and environmental triggers. After puberty, the prevalence of migraine in women is three times higher than in men and >50% of females suffering from migraine report a menstrual association, suggesting hormonal fluctuations can influence the risk of migraine attacks. It has been hypothesized that the drop in estrogen during menses is an important trigger for menstrual migraine. Catechol-O-methyltransferase (COMT) and Cytochrome P450 (CYP) enzymes are involved in estrogen synthesis and metabolism. Functional polymorphisms in these genes can influence estrogen levels and therefore may be associated with risk of menstrual migraine. In this study we investigated four single nucleotide polymorphisms in three genes involved in estrogen metabolism that have been reported to impact enzyme levels or function, in a specific menstrual migraine cohort. 268 menstrual migraine cases and 142 controls were genotyped for rs4680 in COMT (Val158Met), rs4646903 and rs1048943 in CYP1A1 (T3801C and Ile462Val) and rs700519 in CYP19A1 (Cys264Arg). Neither genotype nor allele frequencies for the COMT and CYP SNPs genotyped were found to be significantly different between menstrual migraineurs and controls by chi-square analysis (P>0.05). Therefore we did not find association of functional polymorphisms in the estrogen metabolism genes COMT, CYP1A1 or CYP19A1 with menstrual migraine. Further studies are required to assess whether menstrual migraine is genetically distinct from the common migraine subtypes and identify genes that influence risk.
偏头痛是一种常见的、使人丧失能力的头痛疾病，受多种基因和环境触发因素影响。青春期后，女性偏头痛的患病率比男性高两倍，超过50%的偏头痛女性报告偏头痛与月经有关，这表明激素波动会影响偏头痛发作的风险。据推测，月经期间雌激素水平下降是月经性偏头痛的一个重要触发因素。儿茶酚-O-甲基转移酶（COMT）和细胞色素P450（CYP）酶参与雌激素的合成和代谢。这些基因中的功能多态性会影响雌激素水平，因此可能与月经性偏头痛的风险有关。在本研究中，我们在一个特定的月经性偏头痛队列中，调查了参与雌激素代谢的三个基因中的四个单核苷酸多态性，这些多态性据报道会影响酶水平或功能。对268例月经性偏头痛病例和142例对照进行基因分型，检测COMT基因的rs4680（Val158Met）、CYP1A1基因的rs4646903和rs1048943（T3801C和Ile462Val）以及CYP19A1基因的rs700519（Cys264Arg）。通过卡方分析，未发现月经性偏头痛患者和对照之间COMT和CYP单核苷酸多态性的基因型频率或等位基因频率有显著差异（P>0.05）。因此，我们未发现雌激素代谢基因COMT、CYP1A1或CYP19A1中的功能多态性与月经性偏头痛有关。需要进一步研究来评估月经性偏头痛在遗传上是否与常见偏头痛亚型不同，并确定影响风险的基因。
