Human aquaporin 4 gene polymorphisms in Chinese patients with neuromyelitis optica

•Polymorphisms in the AQP4 coding region are unlikely to confer NMO susceptibility.•Considerable variation in the noncoding regions of AQP4 exists in Chinese.•3′ UTR of AQP4 presents several polymorphic sites affecting NMO risk in Chinese.

ObjectiveTo investigate the association between aquaporin 4 (AQP4) gene polymorphisms and Chinese patients with neuromyelitis optica (NMO).Methods122 consecutive anti-AQP4 autoantibody (NMO-IgG) seropositive cases were enrolled for gene sequencing. Furthermore, ten SNPs were selected and genotyped for a case-control association analysis on 208 cases and 204 healthy subjects.Results14 novel SNPs were identified, while there were no nonsynonymous mutations and their frequency was low. The heterozygous genotype at two 3′ UTR SNPs was significantly higher in cases than controls: the A/T genotype of SNP rs1058424 (54.81% vs. 42.65%, padjusted = 0.024, OR = 1.670, 95% CI = 1.071-2.605) and the C/T genotype of SNP rs3763043 (53.85% vs. 42.65%, padjusted = 0.028, OR = 1.638, 95% CI = 1.054-2.545). Moreover, the 3′ UTR haplotype ATATGGAT may be protective for NMO (7.67% vs. 12.18%, p = 0.042).ConclusionsPolymorphisms in the coding region of AQP4 are unlikely to confer NMO susceptibility. However, the 3′ UTR of this gene presents several polymorphic sites that may affect NMO risk in the Chinese.