Association Study Of NTR1, PPP1R1B Gene Polymorphisms With Cognitive Function In Schizophrenia Patients

Objective:To explore the association between the NTR1gene, PPPIRIB gene polymorphisms and the verbal memory, visuospatial memory, execution function, information processing speed, psychomotor speed, perception transformation in schizophrenia patients.Methods:108drug-naive, first-episode schizophrenia patients and129healthy Chinese-Han were recruited. The cognitive function of all subjects were elevated by Hopkins Verbal Learning Test-Revised (HVLT-R), Brief Visuospatial Memory Test-Revised (BVMT-R), Wisconsin Card Sorting Test-64(WCST), Wechsler Memory Scale,3rd ed,WMS-III, spatial span subtest (SST), Trail Making Test, Part A (TMT-A) and Stroop Color/Word Test (Stroop). All schizophrenia patients were elevated by Positive and Negative Syndrome Scale (PANSS). Peripheral venous blood were collected from all subjects. Genotyping for six SNPs, including rs6090453C/Q rs6011914C/G, rs2427422A/G of NTR1gene and rs3764352A/G, rs879606A/G, rs12601930C/T of PPPIRIB gene, was analyzed by using a PCR and a restriction fragment length polymorphism analysis.Results:The genotype distribution of the rs6090453C/G, rs6011914C/G, rs2427422A/G in NTR1gene and the rs3764352A/G, rs879606A/G in PPPIRIB gene single nucleotide polymorphisms did not deviate from Hardy-Weinberg equilibrium in the schizophrenia and healthy Chinese-Han groups (All P values more than0.05). The genotype distribution of the rs12601930C/T in PPP1R1B gene single nucleotide polymorphisms deviated from Hardy-Weinberg equilibrium in the healthy and schizophrenia groups (P<0.001, P=0.004), and was similar to those observed in another sample from the Chinese-Han populations (http://www.ncbi.nlm.nih.gov)(Χ2.425,4.301, P=0.109,0.116, respectively). The genotype distributions of NTR1gene rs2427422A/G, rs6090453C/G, rs6011914C/G and PPP1R1B gene rs3764352A/G, rs879606A/G, rs12601930C/T were similar between schizophrenia and healthy Chinese-Han groups (All P values more than0.05). The all scores of HVLT-R, SST, Stroop, TMT-A and recall total score, delay recall score of BVMT-R, Perseverative Responses, Nonperseverative Errors of WCST of schizophrenia patients were worse than that of healthy Chinese-Han subjects(All P values less than0.05). Using ANCOVA with PANSS total number, course of disease, age, educated years, gender as covariates, patients with the genotype of PPP1R1B rs3764352GG got higher recognition scores of BVMT-R than patients with PPP1R1B rs3764352AA, patients with the genotype of PPP1R1B rs879606GG got higher recognition scores of BVMT-R than patients with PPP1R1B rs879606AA and AG, patients with the genotype of PPP1R1B rs12601930TT got higher recognition scores of BVMT-R than patients with PPP1R1B rs12601930CC; patients with the genotype of PPP1R1B rs3764352AA spent less time to finish TMT-A than patients with PPP1R1B rs3764352GG, patients with the genotype of PPP1R1B rs879606GG spent less time to finish TMT-A than patients with PPP1R1B rs879606AA, patients with the genotype of PPP1R1B rs12601930TT spent less time to finish TMT-A than patients with PPP1R1B rs12601930CC. Using ANCOVA with age, educated years, gender as covariates, healthy subjects with the genotype of NTR1rs2427422AA spent more time to finish TMT-A than healthy subjects with NTR1rs2427422GG and AG, healthy subjects with the genotype of NTR1rs6090453CC spent more time to finish TMT-A than healthy subjects with NTR1rs6090453GG and CG, healthy subjects with the genotype of PPP1R1B rs3764352AA spent more time to finish TMT-A than patients with PPP1R1B rs3764352GG, healthy subjects with the genotype of PPP1R1B rs879606AA spent more time to finish TMT-A than healthy subjects with PPP1R1B rs879606GG; healthy subjects with the genotype of PPP1R1B rs879606AA got more words total of Stroop test than healthy subjects with PPP1R1B rs879606GG; healthy subjects with the genotype of PPP1R1B rs12601930CC got higher total of SST than healthy subjects with PPP1R1B rs12601930TT.Conclusion:1. There are significant differences in the outcomes of cognitive functions between the schizophrenia and healthy Chinese-Han groups.2. NTR1gene rs2427422A/G, rs6090453C/G polymorphisms and PPP1R1B gene rs3764352A/G, rs879606A/G, rs12601930C/T polymorphisms were significantly associated with performance of several cognitive functions in Chinese-Han population.3. In Chinese-Han schizophrenia, patients who carried with the genotypes of PPP1R1B rs3764352AA, PPP1R1B rs879606AA and AG, PPP1R1B rs12601930CC had worse visuospatial memory, patients who carried with the genotypes of PPP1R1B rs3764352GG, PPP1R1B rs879606AA, PPP1R1B rs12601930CC had worse psychomotor velocity and cognitive ranking capability.