Association of nitric oxide synthase 1 adaptor protein gene polymorphisms with schizophrenia in a Chinese Han population

Indian J Psychiatry. 2022 Mar-Apr;64(2):130-137. doi: 10.4103/psychiatry.IndianJPsychiatry_278_19. Epub 2022 Mar 24.

Abstract

Introduction: Previous studies have analyzed the association between nitric oxide synthase 1 adaptor protein (NOS1AP) polymorphisms and schizophrenia; however, the results were inconsistent and there was a lack of evidence in a larger sample of Chinese Han population.

Subjects and methods: We decided to determine the association between four NOS1AP single-nucleotide polymorphisms (i.e., rs1858232A/G, rs4531275C/T, rs4657178C/T, and rs6704393C/T) and schizophrenia in northern Chinese Han population (350 patients and 522 controls) using restriction fragment length polymorphism.

Results: Between schizophrenia group and healthy group, the genotype and allele frequencies for rs1858232A/G differed significantly (χ 2 = 6.256, 4.145; P = 0.044, 0.045), but neither genotype nor allele frequencies of rs4531275C/T differed significantly. The genotype frequencies for rs4657178C/T and rs6704393C/T differed significantly (χ 2 = 19.782, 12.683; P < 0.01, P = 0.002) between schizophrenia group and healthy group. In the gender-specific analysis, we found statistically significant difference in genotype frequencies between patients and controls in both subgroups for rs4657178C/T (χ 2 = 9.356, 9.585; P = 0.009, 0.008). There was also a significant difference in the genotype frequency between patients and controls in male subgroup for rs6704393C/T (χ 2 = 8.800, P = 0.012). In the haplotype analysis, only the TCT haplotype frequency of rs6704393C/T, rs4531275C/T, and rs4657178C/T differed significantly between patients and controls in total population (χ 2 = 5.215, P = 0.022).

In conclusion: Individuals with G allele of rs1858232A/G and C allele of rs4657178C/T which may be risk factors for schizophrenia should be given more attention, and also to individuals with the TCT haplotype, who are more likely to have schizophrenia. These results provide novel evidence for an association between NOS1AP polymorphisms and schizophrenia.

Keywords: Chinese; nitric oxide synthase; nitric oxide synthase 1 adaptor protein; polymorphism; schizophrenia.