嗅觉相关SNP及环境因素对长寿人群认知功能的影响

Effects of the Interaction Between Olfaction-associated Single Nucleotide Polymorphism and Environmental Factors on the Cognitive Impairment in Long-lived Population

关键词:  嗅觉  单核苷酸多态性  认知障碍  基因-环境交互作用  长寿

Key words:  olfaction  single nucleotide polymorphism  cognitive impairment  gene-environment interaction  long-lived

摘要:

为探讨OR7D4、OR7E24、OR9Q1、SNCA 4个基因上7个与嗅觉相关的单核苷酸多态性(Single Nucleotide Polymorphism，SNP)及其与环境因素的交互作用对广西红水河流域长寿人群认知功能的影响，本研究采用改进的多重高温连接酶检测反应(improved Multiplex Ligation Detection Reaction,iMLDR)方法对红水河流域长寿组(283例)、子女组(296例)、当地组(326例)、贺州组(286例)的SNP进行基因分型。首先结合卡方检验和非条件性Logistic回归分析来评估各SNP基因型和其等位基因在4组人群中的频率分布情况以及与认知障碍(Cognitive Impairment,CI)的相关性。然后通过连锁不平衡分析，构建单倍型了解各基因位点间的内在交互情况。最后利用广义多因子降维分析方法(GMDR)进一步分析基因-环境交互作用对长寿人群CI的影响。结果表明，OR9Q1 rs2245676、OR7D4 rs61729907基因型及其等位基因的频率分布情况在长寿组和贺州组之间存在明显差异(P＜0.05)。在长寿组中，携带OR7E24 rs2240927 T等位基因的个体患CI的风险比携带C等位基因的明显降低(P＜0.05)。长寿组和当地组中OR7E24单倍型T-C会增加CI的发病风险，当地组中OR7E24单倍型C-T以及子女组中OR9Q1单倍型G-T会降低CI的发病风险。OR7D4单倍型G-C会增加长寿组、当地组CI的发病风险(P＜0.05)。长寿人群中OR7E24 rs2240927、OR7E24 rs12608694、SNCA rs894278之间存在SNP-SNP交互作用；OR7D4 rs61729907、嗅觉与腰臀比(Waist-to-hip Ratio,WHR)之间存在SNP-环境交互作用；OR7D4 G-C、嗅觉、甘油三酯、高密度脂蛋白胆固醇之间存在单倍型-环境交互作用(P＜0.05)。综上，红水河流域长寿人群嗅觉相关基因的多态性与外地人群存在明显差异，部分SNP之间及基因-环境的交互作用对该长寿群体的认知衰老产生一定的影响。

Abstract:

To explore the effects of seven olfactory-related Single Nucleotide Polymorphism (SNP) on OR7D4, OR7E24, OR9Q1 and SNCA genes and their interaction with environmental factors on the cognitive function of long-lived population in Hongshui River Basin, the improved Multiplex Ligation Detection Reaction (iMLDR) method was used to genotype the SNP of the long-lived group (283 cases), the offspring group (296 cases), the local group (326 cases) and the Hezhou group (286 cases) in the Hongshui River Basin in this study. Firstly, chi-square test and unconditional logistic regression were used to analyze the frequency distribution of SNP genotypes and their alleles in the four groups and their correlation with Cognitive Impairment (CI). Then, linkage disequilibrium analysis was performed to construct haplotypes for investigating the underlying interactions among genetic loci. Finally, the Generalized Multi-factor Dimensionality Reduction analysis (GMDR) was used to further analyze the effect of gene-environment interaction on CI in long-lived population. The results showed that:there were significant differences in the frequency distribution of OR9Q1 rs2245676,OR7D4 rs61729907 genotypes and its alleles between the long-lived group and the Hezhou group (P<0.05). In the long-lived group, the risk of CI in individuals carrying the OR7E24 rs2240927 T allele was significantly lower than that of the C allele (P<0.05). In the long-lived group and local group,OR7E24 haplotype T-C would increase the risk of CI;in the local group,OR7E24 haplotype C-T and the children group OR9Q1 haplotype G-T would reduce the risk of CI.OR7D4 haplotype G-C would increase the risk of CI in the long-lived group and local group (P<0.05). There were SNP-SNP interactions among OR7E24 rs2240927,OR7E24 rs12608694 and SNCA rs894278 in the long-lived population.There was a SNP-environment interaction between OR7D4 rs61729907,olfactory and Waist-to-hip Ratio (WHR). There was a haplotype-environment interaction between OR7D4 G-C,olfaction,triglyceride,and high-density lipoprotein cholesterol (P<0.05). In summary,there are significant differences in the polymorphisms of olfactory-related genes between the long-lived population in the Hongshui River Basin and the non-local population.The interaction between some SNPs and the interaction between gene and the environment have a certain effect on the cognitive aging of the long-lived population.