Drug Discovery Lab, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education, Kelambakkam, Tamil Nadu, 603103, India.
Genetics Lab, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education, Chettinad Health City, Kelambakkam, Tamil Nadu, 603103, India.
Neuromolecular Med. 2017 Sep;19(2-3):452-461. doi: 10.1007/s12017-017-8460-z. Epub 2017 Aug 9.
Schizophrenia is a complex psychiatric disorder characterized by memory impairments with delusions and hallucinations. Several investigations have focused on determining the association between NOS1 (nitric oxide synthase-1) polymorphisms and risk of schizophrenia (SZ). However, the association of rs2682826, rs3782206, rs499776, rs3782219, rs41279104, rs3782221, rs1879417, rs4767540, rs561712, and rs6490121 polymorphisms with schizophrenia remains inconclusive. We performed a systematic meta-analysis for each polymorphism to determine its association with SZ by calculating their pooled odds ratio and 95% confidence intervals. The heterogeneity between studies was evaluated using Cochran's Q test to adopt random effects or fixed effects model. Based on our analysis, the rs3782206 polymorphism showed a strongest association with schizophrenia in allelic OR 1.15 (95% CI [1.05-1.25]), homozygote OR 1.35 (95% CI [1.09-1.66]), dominant OR 1.16 (95% CI [1.04-1.29]), and recessive OR 1.29 (95% CI [1.05-1.58]) models in Asian population. Similarly, in Caucasian population, the rs499776 polymorphism attributes risk association in homozygote OR 0.70 (95% CI [0.50-0.98]), dominant OR 3.57 (95% CI [2.34-5.27]), and recessive models OR 0.68 (95% CI [0.50-0.93]) with schizophrenia. Further, the sensitivity analysis was carried out based on leave-one-out method to confirm the reliability of the analysis. Overall, our meta-analysis demonstrates the significance of NOS1 genetic variants that are functionally associated with cognitive and neuropsychiatric symptoms of schizophrenia.
精神分裂症是一种复杂的精神疾病,其特征是记忆障碍伴有妄想和幻觉。多项研究集中在确定一氧化氮合酶-1(NOS1)多态性与精神分裂症(SZ)风险之间的关联。然而,rs2682826、rs3782206、rs499776、rs3782219、rs41279104、rs3782221、rs1879417、rs4767540、rs561712 和 rs6490121 多态性与精神分裂症之间的关联仍存在争议。我们对每种多态性进行了系统的荟萃分析,通过计算其合并优势比和 95%置信区间来确定其与 SZ 的关联。使用 Cochran's Q 检验评估研究之间的异质性,以采用随机效应或固定效应模型。根据我们的分析,rs3782206 多态性在等位基因 OR 1.15(95%CI [1.05-1.25])、纯合子 OR 1.35(95%CI [1.09-1.66])、显性 OR 1.16(95%CI [1.04-1.29])和隐性 OR 1.29(95%CI [1.05-1.58])模型中与亚洲人群的精神分裂症最强相关。同样,在白种人群中,rs499776 多态性在纯合子 OR 0.70(95%CI [0.50-0.98])、显性 OR 3.57(95%CI [2.34-5.27])和隐性模型 OR 0.68(95%CI [0.50-0.93])中与精神分裂症相关。此外,我们还进行了基于遗漏值方法的敏感性分析,以确认分析的可靠性。总的来说,我们的荟萃分析表明,NOS1 遗传变异与精神分裂症的认知和神经精神症状具有功能相关性,具有重要意义。