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A genetic study of the NOS3 gene for ischemic stroke in a Chinese population
Danhua Du1*, Peng Gao1*, Linsen Hu1, Yumei Yang1, Feng Wang1, Lin Ye1, Xuan Zhang1, Ming Chang1, Jiexu Zhao1, Jiang Wu1, Ian L Megson2, Jun Wei2
1Research Centre for Neuroscience and Department of Neurology, First Hospital, Jilin University, Changchun, China; 2Genetics and Immunology Group, Department of Diabetes, UHI Millennium Institute, Inverness, UK; *Danhua Du and Peng Gao contributed equally to this work
Abstract: We recruited 560 unrelated patients with ischemic stroke and 153 unrelated controls to undertake a genetic analysis for association between the NOS3 gene and ischemic stroke. All the subjects were Chinese of Han descent. Because the NOS3 gene spans about 21 kb of DNA and contains 26 exons, we selected a single nucleotide polymorphism (SNP) rs3918181, an A to G base change located in intron 14 of the gene, as a DNA marker. PCR-based restriction fragment length polymorphism analysis was applied to genotype rs3918181 (RsaI site). The chi-square (χ2) goodness-of-fit test showed that the genotypic distributions of the marker were not deviated from Hardy-Weinberg equilibrium in both the patient group (χ2 = 0.166, p = 0.684) and the control group (χ2 = 0.421, p = 0.517). The cocaphase analysis showed allelic association of rs3918181 with ischemic stroke in males (χ2 = 4.04, p = 0.044, OR = 1.43, 95% CI 1.01∼2.02) and frequency of allele A was significantly higher in male patients than male control subjects. The χ2 test revealed genotypic association between rs3918181 and ischemic stroke in males (χ2 = 4.26, df = 1, p = 0.039, OR = 1.61, 95% CI 1.02∼2.53) but not in females. The present work suggests that rs3918181 is associated with ischemic stroke in male patients. This finding gives further evidence in support of the eNOS association with ischemic stroke in the Chinese population.
Keywords: eNOS, gene, single nucleotide polymorphisms (SNPs), ischemic stroke
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