Lea R A, Curtain R P, Shepherd A G, Brimage P J, Griffiths L R
Genomics Research Centre, School of Health Science, Griffith University, Gold Coast, Queensland, Australia.
Am J Med Genet. 2001 Jan 8;105(1):110-3.
Migraine is a debilitating disorder affecting approximately 12% of Caucasian populations. The disease has a large genetic component, although at present the type and number of genes involved is unclear. Candidate gene studies may be useful strategies for identifying genes involved in complex diseases such as migraine, especially if the gene being examined contributes only a minor effect to the overall phenotype. Nitric oxide (NO) is emerging as a key molecule affecting the pain associated with migraine. Since NO synthase (NOS) enzymes catalyze the synthesis of NO, the genes that code for these enzymes are good candidates for migraine molecular genetic analysis. This study investigated the role of a functionally relevant bi-allelic tetranucleotide polymorphism located in the promoter region of the human inducible nitric oxide synthase (iNOS) gene in migraine etiology. A large group of migraine affected individuals (n = 261) were genotyped and compared with an age- and sex-matched group of unaffected controls (n = 252). Results of a chi-squared analysis indicated that allele distributions for both migraine cases and controls were not significantly different (chi2 = 1.93, P = 0.16). These findings offer no evidence for an allelic association of the tested iNOS polymorphism with the common forms of the disease and therefore do not support a role for this gene in migraine pathogenesis.
偏头痛是一种使人衰弱的疾病,影响着约12%的白种人。该疾病具有很大的遗传成分,尽管目前涉及的基因类型和数量尚不清楚。候选基因研究可能是识别参与偏头痛等复杂疾病的基因的有用策略,特别是如果所检测的基因对整体表型仅产生微小影响。一氧化氮(NO)正成为影响与偏头痛相关疼痛的关键分子。由于一氧化氮合酶(NOS)催化NO的合成,编码这些酶的基因是偏头痛分子遗传学分析的良好候选基因。本研究调查了位于人类诱导型一氧化氮合酶(iNOS)基因启动子区域的一个功能相关的双等位基因四核苷酸多态性在偏头痛病因中的作用。对一大组偏头痛患者(n = 261)进行基因分型,并与年龄和性别匹配的未受影响对照组(n = 252)进行比较。卡方分析结果表明,偏头痛病例组和对照组的等位基因分布没有显著差异(χ2 = 1.93,P = 0.16)。这些发现没有为所检测的iNOS多态性与该疾病的常见形式之间的等位基因关联提供证据,因此不支持该基因在偏头痛发病机制中的作用。