脯氨酸脱氢酶基因1945(T／C)多态性与精神分裂症的关联研究

Association Study of PRODH 1945(T/C) Polymorphism with Schizophrenia

目的:旨在探讨PRODH基因与汉族人群精神分裂症的时空联系。方法:采用聚合酶链式反应—限制性片断长度多态性方法,分析330例精神分裂症患者和344例正常对照者中PRODH*1945(T／C)多态性的基因型,比较病例组与对照组之间该多态性的基因型及等位基因的频率差异,进一步分析携带不同基因型的精神分裂症患者的发病年龄。结果:与正常对照组相比,精神分裂症患者PRODH*1945(T／C)多态性的基因型(x2=8．171,df=2,p=0．016)和等位基因(C>T,x2=5．249,df=1,p=0．021,OR=1．37,95％CI:0．56-0．96)的频率差异有统计学意义,携带风险等位基因C的精神分裂症患者发病年龄小于携带T者,差异存在弱显著性(CC+CT:20．43+4．71岁,TT:22．57±5．23岁,t=-2．173,p=0．045)。结论:PRODH*1945(T／C)基因多态性可能参与精神分裂症发病机制及影响精神分裂症的发病年龄。

Objective： Previous studies have reported genetic linkage evidence for a candidate gene of schizophrenia on chromosome 22q11. Recently, the proline dehydrogenase （PRODH） gene, located in the most centromeric part of the 22q11 microdeletion region, has been reported to be strongly associated with schizophrenia from three sets of independent samples and the most significant evidence for association was derived from a single nucleotide polymorphism - PRODH＊1945（T/C ）. In the present study, we proposed to explore the association of PRODH＊1945 （T/C） polymorphism with schizophrenia and age of onset in Chinese Han population. Methods： Using the polymerase chain reaction restriction fragment length polymorphism （PCR-RFLP）, we examined the genotypes of 330 schizophrenic patients and 344 healthy controls. Deviation of the genotype counts from the Hardy-Weinberg equilibrium was tested by using a chi-square goodness-of-fit test. With the chi-square tests, the frequencies of genotypes and alleles of this polymorphism were compared between the case and control groups. Then the age of schizophrenic patients at onset were compared between carriers with C and T alleles by using the t-test. Results： Genotype frequencies of the PRODH＊1945 （T/C） in schizophrenia and healthy control groups did not show significant deviations from Hardy □ Weinberg equilibrium. Compared with the healthy control group, the schizophrenic patients showed significant difference in frequencies of genotypes （x^2=8.171, df=2, p=0.016） or alleles （C〉T, x^2=5.249, df=1, p=0.021, OR=1.37, 95%CI： 0.56-0.96） of PRODH＊1945 （T/C）. The age of schizophrenic patients at onset with risk allele C carriers were significandy lower than those with T allele （CC＋CT： 20.43±4.71yrs, TT： 22.57±5.23 yrs, t = 2.173, p = 0.045）. Conclusion： Our results suggest that the 1945 （T/C） polymorphism of the proline dehydrogenase gene is likely to play a major role in the susceptibility to schizophrenia and may influence the age of onset in Chinese Han population.