子宫内膜癌及非典型增生患者血清载脂蛋白AI水平及其模拟肽L4F对子宫内膜癌细胞增殖的抑制作用

 目的 探讨在中国汉族人群中精神分裂症（schizophrenia，SCZ）患者中并发2型糖尿病（type 2 diabetes mellitus，T2DM）与五羟色胺2C受体（serotonin 2C receptor，5-HTR2C）基因多态性（rs2192371、rs5988072）的关联性。方法 纳入服用氯氮平伴有T2DM（共病组257例）或不伴有T2DM （单纯SCZ组288例）的长期住院SCZ患者，单纯T2DM患者（单纯T2DM组264例）以及正常人群（对照组625例）为研究对象，采用Taqman基因分型技术对5-HTR2C基因的单核苷酸多态性（single nucleotide polymorphism，SNP）位点（rs2192371、rs5988072）进行基因分型，比较各研究组的等位基因、基因型及单体型分布频率有无差异。结果 （1）单位点分析显示：共病组与对照组比较，rs2192371（χ²=19.799，df=2，P<0.001;χ²=7.437，df=1，P=0.006）和rs5988072 （χ²=28.682，df=2，P<0.001;χ²=24.127，df=1，P<0.001）基因型频率和等位基因频率分布差异均有统计学意义;单纯T2DM与对照组比较，rs2192371基因型频率分布差异有统计学意义（χ²=13.715，df=2，P=0.001），而等位基因频率分布差异无统计学意义，rs5988072等位基因和基因型频率分布差异均有统计学意义（χ²=11.378，df=2，P=0.003;χ²=7.142，df=1，P=0.007）。单纯SCZ组与对照组相比，rs2192371基因型频率及等位基因频率分布差异均无统计学意义（P>0.05），rs5988072基因型频率分布差异为边缘性（χ²=6.026，df=2，P=0.049），而等位基因频率分布虽然有差异（χ²=4.964，df=1，P=0.025），但经过Bonforrnie校正后无差异。而在SCZ患者中，共病组与单纯SCZ组相比，rs2192371 （χ²=11.279，df=2，P=0.003;χ²=8.061，df=1，P=0.004）和rs5988072 （χ²=7.013，df=2，P=0.030;χ²=5.931，df=1，P=0.014）基因型频率和等位基因频率分布差异均有统计学意义。（2）单体型分析显示：共病组和单纯SCZ组比较，由rs2192371-rs5988072组成的单体型AC （OR=1.351，χ²=5.841，P=0.015）和GT （OR=0.692，χ²=7.592，P=0.004）差异有统计学意义，单体型AT差异无统计学意义。共病组和单纯T2DM组比较，两组间单体型AC、GT和AT差异均无统计学意义。结论 在中国汉族人群中，SCZ并发T2DM与5-HTR2C基因多态性（rs2192371、rs5988072）存在关联，其可能是SCZ患者伴发T2DM的易感基因。

Association between 5-HTR2C gene polymorphisms and schizophrenia with comorbid type 2 diabetes mellitus

Objective To investigate the association between schizophrenia (SCZ) with type 2 diabetes mellitus (T2DM) and serotonin 2C receptor (5-HTR2C) gene polymorphism (rs2192371,rs5988072) in Chinese Han population.Methods Long-term hospitalized SCZ patients taking clozapine with T2DM (comorbidity group,n=257),SCZ patients without T2DM (SCZ group,n=288),T2DM patients (T2DM group,n=264) and healthy control group (HC group,n=625) were enrolled.The single nucleotide polymorphism (SNP) loci (rs2192371,rs5988072) of 5-HTR2C gene were genotyped by Taqman genotyping technique.The allele,genotype and haplotype distribution frequency of each group were compared.Results (1) Single-locus analysis showed that there were significant differences in genotype and allele frequency between the comorbidity group and HC group in rs2192371 (χ²=19.799,df=2,P<0.001;χ²=7.437,df=1,P=0.006) and rs5988072 (χ²=28.682,df=2,P<0.001;χ²=24.127,df=1,P<0.001).There was significant difference in the frequency distribution of rs2192371 genotypes between T2DM and HC group (χ²=13.715,df=2,P=0.001),but there was no significant difference in the distribution of allele frequency.There were significant differences in the distribution of rs5988072 allele and genotype frequency (χ²=11.378,df=2,P=0.003;χ²=7.142,df=1,P=0.007).There was no significant difference in the distribution of rs2192371 genotype frequency and allele frequency between SCZ and HC group,while the difference of genotype frequency distribution of rs5988072 was marginal (χ²=6.026,df=2,P=0.049).Although there was significant difference in allele frequency distribution (χ²=4.964,df=1,P=0.025),there was no significant difference after Bonforrnie correction.In patients with schizophrenia,there were significant differences in the distribution of genotype and allele frequencies of rs2192371 (χ²=11.279,df=2,P=0.003;χ²=8.061,df=1,P=0.004) and rs5988072 (χ²=7.013,df=2,P=0.030;χ²=5.931,df=1,P=0.014) between the comorbidity group and the SCZ group.(2) haplotype analysis showed that there was significant difference in haplotype AC (OR=1.351,χ²=5.841;P=0.015) and GT (OR=0.692,χ²=7.592,P=0.004) between comorbidity group and SCZ group,but there was no significant difference in haplotype AT.There was no significant difference in haplotype AC,GT and AT between comorbidity group and T2DM group.Conclusion The comorbidity of type 2 diabetes mellitus in schizophrenia is associated with 5-HTR2C gene polymorphism (rs2192371,rs5988072) in Chinese Han population,which may be the susceptibility gene of schizophrenia with type 2 diabetes mellitus.