嗅觉相关SNP及环境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 longevity 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  Longevity

摘要:

为探讨OR7D4、OR7E24、OR9Q1、SNCA 4个基因上的7个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红水河流域长寿人群认知功能的影响，本研究采用多重酶连接反应（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回归分析各SNPs基因型和等位基因在4组人群中的频率分布情况以及与认知障碍的相关性。再通过Haploview 4.2软件分析各位点间的连锁不平衡（LD），构建单倍型了解基因间的交互情况。最后利用广义多因子降维分析方法（GMDR）进一步分析基因-环境的交互作用对长寿人群认知障碍（Cognitive Impairment, CI）的影响。结果表明，（1）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）。（2）在长寿组中，携带OR7E24 rs2240927 T等位基因的个体患CI的风险比C等位基因明显减低（P＜0.05）。（3）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发病风险。OR7D4 单倍型G-C会增加长寿组、当地组CI的风险（P＜0.05）。（4）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、TG、HDL-C之间存在单倍型-环境的交互作用（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SNPs之间及部分SNPs与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。 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

Abstract:

Objectives To investigate the effects of olfaction related single nucleotide polymorphism (SNP) of OR7D4, OR7E24, OR9Q1, SNCA on blood glucose levels in long-lived population in Bama region of Guangxi. Methods SNPscanTM multiplex SNP genotyping method was adopted to genotype the SNP of the long-lived group (283 cases), the Offspring group (296 cases), the control group (326 cases), and the Hezhou group (286 cases). Firstly，Chi-square test and unconditional logistic regression analysis were used to evaluate the distribution of each SNP genotype and allele frequency in the four groups of people and their correlations with the onset of cognitive impairment. Then, The linkage disequilibrium (LD) between each locus was analyzed by Haploview 4.2 software to understand the interaction between haplotypes and the interaction between genes. Finally, The generalized multifactor dimensionality reduction analysis method (GMDR) was used to further analyze the interaction between genes and environment on cognitive impairment (Cognitive impairment, CI) in the long-lived population. Results 1. There were significant differences in the distribution frequencies of OR9Q1 rs2245676 and OR7D4 rs61729907 genotypes and alleles between the long-lived group and the Hezhou group (P < 0.05); 2. In the long-lived group, individuals carrying the OR7E24 rs2240927 T allele had a lower risk of CI than those carrying the C allele, and the additive model TT and recessive model TT genotypes had a lower risk of CI (P < 0.05); 3. In the long-lived group and the control group, OR7E24 haplotype T-C would increase the risk of CI; in the local group, OR7E24 haplotype C-T and the Offspring 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 the control group (P < 0.05); 4. Among the long-lived population, there were SNP-SNP interactions between OR7E24 rs2240927 and rs12608694 and SNCA rs894278; SNP-environment interactions between OR7D4 rs61729907 and olfaction and WHR; and haplotype-environment interactions between OR7D4 G-C, olfaction, TG, and HDL-C (P < 0.05). Conclusion The polymorphisms of genes related to olfaction, as well as the gene-environment interaction, are associated with cognitive impairment in the long-lived population.