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利用传递不平衡检验研究白细胞介素1基因复合体功能多态性与精神分裂症之间的关联。

An Association Between Functional Polymorphisms of the Interleukin 1 Gene Complex and Schizophrenia Using Transmission Disequilibrium Test.

作者信息

Kapelski Pawel, Skibinska Maria, Maciukiewicz Malgorzata, Pawlak Joanna, Dmitrzak-Weglarz Monika, Szczepankiewicz Aleksandra, Zaremba Dorota, Twarowska-Hauser Joanna

机构信息

Psychiatric Genetics Unit, Department of Psychiatry, Poznan University of Medical Sciences, Szpitalna 27/33, 60-572, Poznan, Poland.

Pharmacogenetics Research Clinic, Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, 250 College Street, Toronto, ON, M5T1R8, Canada.

出版信息

Arch Immunol Ther Exp (Warsz). 2016 Dec;64(Suppl 1):161-168. doi: 10.1007/s00005-016-0434-6. Epub 2017 Jan 12.

Abstract

IL1 gene complex has been implicated in the etiology of schizophrenia. To assess whether IL1 gene complex is associated with susceptibility to schizophrenia in Polish population we conducted family-based study. Functional polymorphisms from IL1A (rs1800587, rs17561, rs11677416), IL1B (rs1143634, rs1143643, rs16944, rs4848306, rs1143623, rs1143633, rs1143627) and IL1RN (rs419598, rs315952, rs9005, rs4251961) genes were genotyped in 143 trio with schizophrenia. Statistical analysis was performed using transmission disequilibrium test. We have found a trend toward an association of rs1143627, rs16944, rs1143623 in IL1B gene with the risk of schizophrenia. Our results show a protective effect of allele T of rs4251961 in IL1RN against schizophrenia. We also performed haplotype analysis of IL1 gene complex and found a trend toward an association with schizophrenia of GAGG haplotype (rs1143627, rs16944, rs1143623, rs4848306) in IL1B gene, haplotypes: TG (rs315952, rs9005) and TT (rs4251961, rs419598) in IL1RN. Haplotype CT (rs4251961, rs419598) in IL1RN was found to be associated with schizophrenia. After correction for multiple testing associations did not reach significance level. Our results might support theory that polymorphisms of interleukin 1 complex genes (rs1143627, rs16944, rs1143623, rs4848306 in IL1B gene and rs4251961, rs419598, rs315952, rs9005 in IL1RN gene) are involved in the pathogenesis of schizophrenia, however, none of the results reach significance level after correction for multiple testing.

摘要

白细胞介素1(IL1)基因复合体与精神分裂症的病因有关。为了评估IL1基因复合体是否与波兰人群中精神分裂症的易感性相关,我们进行了基于家系的研究。对143个精神分裂症三联体进行了IL1A(rs1800587、rs17561、rs11677416)、IL1B(rs1143634、rs1143643、rs16944、rs4848306、rs1143623、rs1143633、rs1143627)和IL1RN(rs419598、rs315952、rs9005、rs4251961)基因的功能多态性基因分型。使用传递不平衡检验进行统计分析。我们发现IL1B基因中的rs1143627、rs16944、rs1143623与精神分裂症风险之间存在关联趋势。我们的结果显示IL1RN基因中rs4251961的T等位基因对精神分裂症有保护作用。我们还对IL1基因复合体进行了单倍型分析,发现IL1B基因中的GAGG单倍型(rs1143627、rs16944、rs1143623、rs4848306)、IL1RN基因中的单倍型TG(rs315952、rs9005)和TT(rs4251961、rs419598)与精神分裂症存在关联趋势。发现IL1RN基因中的单倍型CT(rs4251961、rs419598)与精神分裂症相关。在进行多重检验校正后,关联未达到显著水平。我们的结果可能支持白细胞介素1复合体基因多态性(IL1B基因中的rs1143627、rs16944、rs1143623、rs4848306以及IL1RN基因中的rs4251961、rs419598、rs315952、rs9005)参与精神分裂症发病机制的理论,然而,在进行多重检验校正后,没有一个结果达到显著水平。

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