Correlation Between ACE, ApoB, FOXO3A Gene Polymorphism And DNA Methylation And Longevity In Guangxi Bama

Objective: To investigate association between the polymorphisms of Angiotensin converting Enzyme(ACE), Apolipoprotein B(ApoB), FOX03A gene and human longevity in Bama county, and to explore the interaction environment of the longevity district and the genetic polymorphisms of the genes in human longevity.Methods: Based on the primitive record data during the fifth national census in 2000, demography data(≥100 years) of the Bama area was statistical analyzed. The longevity district was measured by the population distribution of longevity to be the top three in Bama (105/105、80/105、76/105),and the non-longevity district was measured by that to be the last or last (21/105、15/105). We collected 177 longevity people aged 90 to 110 from longevity district of Bama county. The controls were composed of five groups. The control group Ⅰ -Ⅲ came from the longevity district, and the control groupⅣ-Ⅴ came from the no-longevity district. The control group I was composed of 121 people who were direct dependents of those in the longevity group. The control groupⅡ was composed of 83 people aged between 80 and 89 years who had their longevity families. The control group III was composed of 140 who had no-longevity history family between 4 and 87 years. The control groupIV was composed of 23 people aged between 90 and 105 years. The control group V was composed of 148 people aged between 48 and 89 years who had no-longevity history family. After getting subjects’ permission, the blood samples were collected and DNA was extracted from them, then detecting the polymorphisms of ACE, APOB, FOXO3A gene with PCR-RFLP and TaqMan SNP Genotyping Assays. All data were performed with x2 statistics and logistic regression analysis by using the software program SPSS. P<0.05 was considered significant.Results: 1 .No significance diviation for the polymorphisms in ACE, APOB and FOXO3A gene for the study population were observed from Hardy-Weinberg Equilibrium (HWE).2.The frequencies of ACE genotype DD,ID,Ⅱ were 9%,43.5%,47.5% in the longevity group, and the frequencies of D,I allele were 30.8%, 69.2%. Both of that were higher than all the controls. No significant differences for the frequencies of genotype and allele of ACE between longevity group and the control group Ⅰ , the control group Ⅱ, the control group Ⅳ. But there were significant differences between longevity group and the control group Ⅲ, the control group Ⅴ. The interaction and confounding among the factors were estimated, the results showed that there was a positive interaction between the ID+DD genotypes and the environment of longevity district.3. In Bama population, X+X+ genotype of ApoB constituted the majority,only two sample showed X+X+ genotype. Compared with the control group Ⅰ ,the control group Ⅱ, the control group Ⅳ, no significant differences for the frequencies of genotype and allele of APOB gene were observed. The frequencies of X+ allele in ApoB gene of the longevity group (6.8%) were higher than the control group Ⅲ and the control group Ⅴ. There were significant differences between longevity group and the control group III, the control group V in the frequencies of X+X-X+X+ genotypes. The interaction and confounding among the factors were estimated, the results showed that there was a positive interaction between the X+X++X+X- genotypes and the environment of the longevity district.4.Except for rs13230810 and rs7762395, the Minor allele frequencies of 6 SNPs for FOXO3A gene in our study population are higher than that in the Chinese Han in Bingjing (according to CHB HapMap data), and significant difference was found between them. Minor allele frequencies of 5 known SNPs in FOXO3A gene were higher in cases than in controls. Frequency of haplotype’AG’ was higher in cases than in controls, and frequency of haplotype’TTTGTC’ was opposite to the former. The interaction and confounding among the factors were estimated, which showed that there was a positive interaction between minority alleles of rs2764264 in FOXO3A gene and the environment of the longevity district. The interaction also be showed between GTC, CT haplotypes and the environment. But TTT haplotype in FOX03A gene might be a risk factor for human longevity. The interaction of them had significant antagonism to longevity.Conclusions: 1 .The polymorphisms of ACE, ApoB and FOXO3A gene would be relevant to Bama’s longevity. Five SNPs and two LD-based haplotypes of FOXO3A gene would be closely correlated with human longevity in Bama area.2. The minor allele of rs2764264 and GTC, CT haplotypes in FOX03A gene, D allele in ACE gene, X+ allele in ApoB gene and the environment of the longevity district might be active factors for human longevity. The interaction of the polymorphisms of ACE, ApoB, FOX03A genes with the environment of the longevity district had synergy of longevity. It showed an additive effect in longevity of Bama. But TTT haplotype in FOXO3A gene might be a risk factor for human longevity. The interaction of them had significant antagonism to longevity.Objective: To find out the correlation between hypermethylation genes and the longevity in Bama county.Methods: 4 DNA pools were built. The first one was made up of 30 longevity people aged 100 to 110. The second one was made up of 30 longevity people aged 90 to 99. The third one was made up of 30 people aged 48 to 75.The last one was made up of 30 people aged 76 to 85. The longevity group comprises the former two pools. The control group comprises the latter two pools. Roche NimbleGen chip was used in scanning of four separated DNA pooling samples. Statistic analysis was performed by MAS system and SPSS software.Results: Significant differences were found with between cases and controls (P<0.01). Microarray data indicated that there were 1616 hypermethylation genes in our study population. In which, 132 genes were showed in the longevity group which might be classified and related to 27 biological functions, and involved in 41 biological pathways, and 1484 genes were showed in the control group which might be classified and related to 28 biological functions, and involved in 154 biological pathways.The hypermethytlation genes were mainly related to the cellular process,physiological process,biological regulation. Diverse signal transduction pathways such as Natural killer cell mediated cytotoxicity, Calcium signaling pathway, Neuroactive ligand-receptor interaction took part in Bama’longevity.Conclusions: The research got a hypermethylation genetic mapping,the gene function classification and analysis of biological pathway which related to the longevity in Bama county. The result provided a primary facie evidence for study on correlation between DNA methylation and longevity.