Lee Hane, Sininger Lauren, Jen Joanna C, Cha Yoon-Hee, Baloh Robert W, Nelson Stanley F
Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Neurogenetics. 2007 Aug;8(3):195-200. doi: 10.1007/s10048-007-0091-3. Epub 2007 Jul 3.
While migraine has been demonstrated to be familial and have genetic contributions, genome-wide linkage analyses and candidate gene studies have highlighted that migraine is genetically complex. Despite substantial efforts, no consistent replication of linkage or association has been reported for common migraine syndromes. Among the candidate genes tested for association with migraine by several groups were female sex hormone genes based on the observation of a much higher incidence of migraine in females. Migraine-associated vertigo (MAV) is a migraine syndrome also much more common in females than males. Because MAV is less common in the general population than migraine or migraine with aura, it may be a better migraine syndrome to detect susceptibility alleles. In this study, we tested the association of two female hormonal genes, progesterone receptor (PGR) and estrogen receptor (ESR1), which were previously reported to be associated with migraine in women. We typed 150 MAV subjects and 145 genomic matched control subjects. One SNP (rs1042838) within PGR, which is in high linkage disequilibrium with the functional PROGINS variant, was significantly associated with MAV (p = 0.0007). Two SNPs (rs2228480 and rs1801132) within ESR1 demonstrated no significant association. No synergistic effect between ESR1 variants and PGR variants was identified.
虽然偏头痛已被证明具有家族性且有遗传因素，但全基因组连锁分析和候选基因研究表明偏头痛在遗传上是复杂的。尽管付出了巨大努力，但尚未有关于常见偏头痛综合征连锁或关联的一致重复报道。在几组测试与偏头痛相关的候选基因中，基于女性偏头痛发病率高得多的观察结果，女性性激素基因被纳入其中。偏头痛相关性眩晕（MAV）是一种偏头痛综合征，在女性中也比男性更为常见。由于MAV在普通人群中比偏头痛或伴有先兆的偏头痛少见，它可能是检测易感等位基因的更好的偏头痛综合征。在本研究中，我们测试了两个女性激素基因，孕酮受体（PGR）和雌激素受体（ESR1）的关联性，这两个基因先前报道与女性偏头痛有关。我们对150名MAV受试者和145名基因组匹配的对照受试者进行了基因分型。PGR内的一个单核苷酸多态性（SNP，rs1042838）与功能性PROGINS变异处于高度连锁不平衡状态，与MAV显著相关（p = 0.0007）。ESR1内的两个SNP（rs2228480和rs1801132）未显示出显著关联。未发现ESR1变异与PGR变异之间存在协同效应。
