Abstract: Objective To study the association between peroxisome proliferator-activated receptor γ 2 (PPAR γ 2) gene polymorphism and the onset of sporadic Alzheimer's disease (SAD). Methods According to the method of case-control study, DNA blood specimens were randomly collected in SAD patients and controls. Polymerase chain reaction (PCR) was performed to proliferate PPARγ2 gene exon B, and sequential method was used to scan the mutational site. Polymorphism in exon B of PPAR γ 2 gene of 310 SAD patients (AD group) and 289 healthy controls (control group) in Chinese Han population were genotyped by PCR-restriction fragment length polymorphism (RFLP). All subjects were genotyped for apolipoprotein E (ApoE) by the methods previously described. Allelic and genotypic distributions in AD group and control group were compared to study the association between the polymorphism and the risk for SAD by Chi-square test. Results Pro12Ala (rs1801282) polymorphism in exon B of PPAR γ 2 gene was detected in the Chinese Han population by direct sequencing. The distribution of the genotype and allele frequencies of rs1801282 all coincided with Hardy-Weinberg equilibrium in SAD patients and controls. There were no significant differences of genotype or allele frequencies in SAD patients between those in controls (P = 0.647, 0.501, respectively). Among those ≥ 75 years old and ApoEε4 allelic gene carrier, the Pro/Ala gene frequency and Ala allelic gene frequnecy in AD group were all higher than those in control group, but the differences were not significant (P > 0.05, for all). There was no association between Pro12Ala polymorphism and SAD after gender, age and ApoE adjustment by Logistic regression (OR = 1.100, 95% CI: 0.580-2.090; P = 0.767). Conclusion This study does not support the association of Pro12Ala polymorphism with SAD in Chinese Han population.

Key words: Alzheimer disease, Peroxisome proliferator-activated receptors, Polymorphism, single nucleotide, Genotype, Alleles, Case-control studies

摘要： 目的   研究过氧化物酶增殖物激活受体γ2（PPAR γ 2）基因rs1801282 位点单核苷酸Pro12Ala 多态性（CCA→GCA）与散发性阿尔茨海默病发病的相关性。方法   采用病例对照研究方法随机采集散发性阿尔茨海默病患者和正常对照者血液DNA 标本，聚合酶链反应扩增PPARγ2 基因外显子B，直接测序法筛查突变位点；根据聚合酶链反应?限制性片段长度多态性对310 例中国汉族散发性阿尔茨海默病患者和289 例正常对照者PPARγ2 基因外显子B 多态性进行分型。结果   PPARγ2 基因外显子B 突变位点筛查发现rs1801282 位点单核苷酸Pro12Ala 多态性，两组受试者基因型和等位基因频率分布均符合Hardy-Weinberg 遗传平衡定律，差异无统计学意义（P = 0.647，0.501）。在≥ 75 岁和携带ApoEε4等位基因的人群中，阿尔茨海默病组患者Pro/Ala 基因型频率、Ala 等位基因频率均高于对照组，但差异无统计学意义（均P > 0.05）；经Logistic 回归模型校正性别、年龄、ApoEε4 等位基因携带状态等影响因素后，未发现多态性位点与散发性阿尔茨海默病的发病具有相关性（OR = 1.100，95%CI：0.580 ~ 2.090；P =0.767）。结论   在中国汉族人群中，PPARγ2 基因rs1801282 位点单核苷酸Pro12Ala 多态性可能与散发性阿尔茨海默病的发病无相关性。

关键词: 阿尔茨海默病, 过氧化物酶体增殖物激活受体, 多态性, 单核苷酸, 基因型, 等位基因, 病例对照研究