精神分裂症与染色体22q11的连锁不平衡研究

Linkage disequilibrium analysis of chromosome 22q11 and schizophrenia

目的 探讨染色体 2 2q11泛有素融合降解 1型蛋白基因 (UFD1L)和腭心面综合征缺失的核定位信号基因 (NLVCF)多态性与精神分裂症的关系。方法 在 138例吉林省汉族精神分裂症患者及其健康父母双亲的核心家系中 ,以聚合酶链反应 (PCR)和限制性片段长度多态 (RFLP)方法对UFD1L基因rs15 4 7931(G/C碱基改变 )和NLVCF基因rs14 7310 9(C/T碱基改变 )单核苷酸多态性 (SNPs)进行检测。应用基于家系的连锁不平衡方法 ,包括单体型相对风险分析 (HRR) ,传递不平衡检验(TDT)及Transmit双位点单体型分析 ,分析基因型数据。结果 ( 1)HRR显示UFD1L基因rs15 4 7931与精神分裂症有关联 ( χ2 =4 2 6 0 ,ν=1,P =0 0 39) ,NLVCF基因rs14 7310 9与精神分裂症无关联 ;( 2 )TDT显示UFD1L基因rs15 4 7931与精神分裂症有连锁和关联 ( χ2 =5 333,ν=1,P =0 0 2 1) ,NLVCF基因rs14 7310 9与精神分裂症无连锁及关联 ;( 3)Transmit双位点单体型分析显示rs15 4 7931～rs14 7310 9单体型与精神分裂症有关联 ( χ2 =9 72 3,ν =3,P =0 0 2 1) ,rs15 4 7931(C)～rs14 7310 9(T)单体型与精神分裂症呈负相关 ( χ2 =6 6 0 7,ν=1,P =0 0 1)。结论 精神分裂症患者UFD1L基因本身或其附近的基因可能与精神分裂症的易感性相关。

Objective To investigate genetic association between schizophrenia and the polymorphisms of ubiquitin fusion degradation 1 like (UFD1L) and nuclear localization signal deleted in velocardiofacial syndrome (NLVCF) genes on chromosome 22q11 in a Chinese Han population Methods All 138 nuclear family trios, including healthy parents and offsprings with schizophrenia were recruited Two single nucleotide polymorphisms (SNPs), rs1547931 (G/C base change) in UFD1L locus and rs1473109 (C/T base change) in NLVCF locus, were detected with the PCR based restriction fragment length polymorphism analysis Linkage disequilibrium methods based on family, including haplotype relative risk (HRR) analysis, transmission disequilibrium test (TDT) and transmit two loci haplotypes analysis were used Results (1) The HRR analysis showed that rs1547931 (χ 2=4 260, ν=1, P= 0 039), but not rs1473109 was associated with schizophrenia (2) The TDT analysis indicated that rs1547931 (χ 2=5 333, ν=1, P= 0 021), but not rs1473109 was associated with schizophrenia (3) The haplotype analysis showed a significant biased transmission of rs1547931 rs1473109 haplotypes from parents to the affected offsprings (χ 2= 9 723, ν=3, P= 0 021), and a negative association between the rs1547931 (C) rs1473109 (T) haplotype and schizophrenia (χ 2=6 607, ν=1, P= 0 01) Conclusions Either the UFD1L gene itself or a locus nearby may confer susceptibility to schizophrenia in this Chinese Han population