酪氨酸羟化酶基因多态性与早发精神分裂症的关联分析

Association analysis of the tyrosine hydroxylase gene polymorphisms with early-onset schizophrenia in Chinese population

目的 探讨中国汉族人群酪氨酸羟化酶（tyrosine hydroxylase,TH）基因多态性与早发精神分裂症的关联性.方法 采用TaqMan荧光探针基因分型技术,检测315例早发精神分裂症患者（患者组,起病年龄＜18岁）和391名健康对照（对照组）TH基因标签单核苷酸多态性rs2070762、rs6356及rs11042978 3个多态位点,并对等位基因、基因型及单体型频率进行比较.结果 （1）患者组与对照组单位点分析显示,rs2070762[x2=1.12,自由度（df）=1,P=0.290;x2 =1.75,df=2,P=0.417]及rs6356（x2=1.71,df=1,P=0.190;x2=2.86,df=2,P=0.239）等位基因和基因型分布差异无统计学意义.rs11042978等位基因分布和基因型分布的差异有统计学意义（x2=4.47,df=1,P =0.034;x2=6.35,df=2,P=0.042）,但经Bonferroni校正检验后,差异无统计学意义（P＞0.05）;（2）单体型分析显示,患者组与对照组比较,由rs2070762-rs6356-rs11042978组成的单体型A-C-G,差异有统计学意义（x2=6.35,P=0.012）,但经Permutation校正检验后,差异无统计学意义（x2=4.84,P=0.104）.结论 在中国汉族人群中酪氨酸羟化酶基因可能不是早发精神分裂症的易患基因.

Objective To investigate the relationship between the tyrosine hydroxylase （TH） gene and early-onset schizophrenia in Chinese Han population. Methods The tag single nucleotide polymorphisms （tag SNPs） rs2070762, rs6356 and rs11042978 in the TH gene were genotyped in 315 early- onset schizophrenics （188 male patients, 127 female patients） and 391 controls subjects （219 males, 172 females）. Single nueleotide polymorphism association and haplotype analysis were performed. Results （1） No statistically significant differences were found in allele or genotype between patients and normal controls for rs2070762（X2 = 1.12, dr= 1, P = 0. 290;X2 = 1.75, dr=2, P =0. 417） and rs6356 （ X2 = 1.71, dr= 1, P = 0. 190; X2 = 2. 86, dr= 2, P = 0. 239）. There were significant differences in allele and genotype frequencies between patients and normal control for rs11042978 allele （ X2 = 4.47, df = 1, P = 0. 034） and genotype （X2 = 6. 35, df= 2, P = 0. 042）, but the difference did not existed after Bonferroni correction in allele frequencies （ P 〉 0. 05 ）. （2） The analysis revealed that there were significant differences between patients and normal control subjects for haplotypes A-C-G of rs2070762-rs6356-rsl1042978 （X2 = 6. 35 ,P = 0. 012）, but the difference did not existed after Permutation test in haplotype frequencies（ X2 = 4. 84, P = 0. 104）. Conclusions The TH gene may not play major roles in the susceptibility to early-onset schizophrenia in Chinese population.