Department of Forensic Medicine, Medical College of Soochow University, Suzhou, Jiangsu, PR China.
DNA Cell Biol. 2011 Feb;30(2):117-22. doi: 10.1089/dna.2010.1102. Epub 2010 Sep 28.
Genes involved in the production of nitric oxide (NO) have been suggested as genetic factors for migraine. It has been studied whether polymorphisms in the genes encoding for different types of NO synthase (NOS) could be involved in the liability to migraine; however, most studies yield negative results. The pentanucleotide repeat microsatellite in the promoter region of inducible NOS (NOS2) shows highly significant differences in allelic frequencies among ethnically diverse populations. Thus, variation in the number of pentanucleotide repeats may have some significance in the predisposition to migraine among different human populations. The aim of this study was to investigate the possible association between pentanucleotide repeat polymorphism and the risk for migraine in Chinese population. We studied the genotypic and allelic frequencies of the pentanucleotide repeat polymorphism in the promoter region of NOS2 in 504 patients with migraine and 512 healthy controls, using polymerase chain reaction amplification and polyacrylamide gel electrophoresis analyses. Comparison of global allele counts between patients and controls showed that the difference was significant (p = 0.0014). The carriage of 9-repeat and 10-repeat alleles was significantly more common in controls, whereas 11-repeat allele was more common in patients after Bonferroni correction for multiple comparisons. A specific analysis of the different cutoffs for number of repeats showed that allelic and genotypic frequencies for the 9-repeat and 10-repeat cutoff were significantly different between cases and controls (p = 0.007 and p = 0.005 for allelic frequencies, respectively; p = 0.0086 and p = 0.0033 for genotypic frequencies, respectively). Our results implied an association between NOS2 pentanucleotide repeat polymorphism and migraine susceptibility in a Chinese population. Considering the significant allelic frequency differences in ethnically diverse populations, further replication studies, especially in ethnically different groups, were necessary to fully establish the role of NOS2 polymorphism in migraine susceptibility.
参与一氧化氮（NO）产生的基因被认为是偏头痛的遗传因素。已经研究了不同类型的一氧化氮合酶（NOS）基因编码中的多态性是否可能与偏头痛的易感性有关；然而，大多数研究结果都是阴性的。诱导型NOS（NOS2）启动子区域的五核苷酸重复微卫星在不同种族的人群中具有高度显著的等位基因频率差异。因此，五核苷酸重复数的变化可能在不同人群中偏头痛的易感性方面具有一定意义。本研究旨在探讨 NOS2 启动子区五核苷酸重复多态性与中国人群偏头痛风险之间的可能关联。我们使用聚合酶链反应扩增和聚丙烯酰胺凝胶电泳分析，研究了 504 例偏头痛患者和 512 例健康对照者 NOS2 启动子区五核苷酸重复多态性的基因型和等位基因频率。患者和对照组之间的全局等位基因计数比较表明，差异具有统计学意义（p=0.0014）。在经过多次比较的 Bonferroni 校正后，9 重复和 10 重复等位基因在对照组中更为常见，而 11 重复等位基因在患者中更为常见。对不同重复数的特定分析表明，9 重复和 10 重复切点的等位基因和基因型频率在病例和对照组之间存在显著差异（等位基因频率分别为 p=0.007 和 p=0.005；基因型频率分别为 p=0.0086 和 p=0.0033）。我们的结果表明，NOS2 五核苷酸重复多态性与中国人群偏头痛易感性之间存在关联。考虑到不同种族人群中存在显著的等位基因频率差异，需要进行进一步的复制研究，特别是在不同种族的人群中，以充分确立 NOS2 多态性在偏头痛易感性中的作用。
