Association of the pentanucleotide repeat polymorphism in NOS2 promoter region with susceptibility to migraine in a Chinese population.

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.