Association Of The Pentanucleotide Repeat Polymorphism In NOS2Promoter Region With Susceptibility To Migraine In A Chinese Population

Background Genes involved in the production of nitric oxide (NO) have beensuggested as genetic factors for migraine. It has been studied whether polymorphisms inthe genes encoding for different types of NO synthase (NOS) could be involved in theliability to migraine; however, most studies yield negative results. The pentanucleotiderepeat microsatellite in the promoter region of inducible NOS (iNOS, NOS2) shows highlysignificant differences in allelic frequencies among ethnically diverse populations. Thus,variation in the number of pentanucleotide repeats may have some significance in thepredisposition to migraine among different human populations.Objective The aim of this study was to investigate the possible association betweenpentanucleotide repeat polymorphism and the risk for migraine in Chinese population.Method We studied the genotypic and allelic frequencies of the pentanucleotiderepeat polymorphism in the promoter region of NOS2in504patients with migraine and512healthy controls, using polymerase chain reaction amplification and polyacrylamidegel electrophoresis analyses.Results Comparison of global allele counts between patients and controls showed thatthe difference was significant (P=0.0014). The carriage of9-repeat and10-repeat alleleswas significantly more common in controls, whereas11-repeat allele was more common inpatients after Bonferroni correction for multiple comparisons. A specific analysis of thedifferent cutoffs for number of repeats showed that allelic and genotypic frequencies forthe9-repeat and10-repeat cutoff were significantly different between cases and controls (P=0.007and P=0.005for allelic frequencies, respectively; P=0.0086and P=0.0033for genotypic frequencies, respectively).Conclusions Our results implied an association between NOS2pentanucleotide repeatpolymorphism and migraine susceptibility in a Chinese population. Considering thesignificant allelic frequency differences in ethnically diverse populations, furtherreplication studies, especially in ethnically different groups, were necessary to fullyestablish the role of NOS2polymorphism in migraine susceptibility.