Correlation Between CETP And UCP2 Genes And Natural Longevity In Xinjiang Hetian Uygur Population

BackgroudAging was attributed to development, genetic default, diseases and the inborn aging processing (IAP). In order to understand how to resist or delay the aging and attain the natural longevity human being owning, scientists proposed the various of mechanisms and theories, which involved oxidative stress, energy metabolism, signal transduction pathway, immune system and so on. Moreover, there were interaction among these mechanisms which affected by genetics. To identify the biological marker related to longevity was important to penetrate into the mechanisms that biomarkers-carriers escaped the common diseases and/or postponed the aging process. At present, the studies focused on genes related to inflammation and immune, insulin/ insulin-like growth factor (IGF-1) signaling pathway, genes related to lipid metabolism and oxidative stress, as well as mitochondrial genome.The centenarian, who represents the extremity of longevity, was the optimal population of researching the human longevity. The quantity and relative ratio of centenarian in Xinjiang Hetian were over the average level of whole country, so Hetian was classified as one of four longevity regions in the world. Furthermore, because of environment, living characteristics, customs and habits, the Uygur who lived in this region became genetic isolation population and belonged to the natural longevity. Thereby, they were the value resource of genetic study about longevity.Besides the common methods which compared the genotype distribution of single polymorphism between the longevities and the controls, the genetic methods of longevity study include the linkage disequilibrium and haplotype analysis, which became increasingly the effective methods of studying the life-span that was the complex phenotype controlled by multiple genes and gene-environment interaction. The linkage disequilibrium and haplotype analysis were valuable to association analysis, especially the association study of complex diseases. ObjectivesTo investigate the association between polymorphisms (promoter-866G/A, A55V and 3' untranslated region I/D) and their haplotype within uncoupling protein-2 (UCP2) gene, as well as polymorphisms (TaqIB, D442G and I405V) and their haplotype within the cholesteryl ester transfer protein (CETP) gene, and natural longevity in Xinjiang Uygur population.Methods191 healthy Uygur individuals over 90 years in Xinjiang Hetian were recruited. And 53 area-, nationality-, gender-matched individuals who had no longevity family history and died in their 75 years were studied as control subjects. Their height, weight, systolic bloodpressure (SBP) and diastolic blood pressure (DBP), serum total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein A (ApoA) and blood glucose (BG) were measured. Genome DNA was extracted from white blood cells. Using polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing technique, we tested the polymorphisms of the polymorphisms of promoter-866G/A, A55V and 3'UTR-I/D within UCP2 gene and TaqIB, D442G and I405V within CETP gene, and performed the linkage disequilibrium and haplotype analysis.ResultsThe study about UCP2 gene polymorphisms showed there was II genotype of 3'UTR-I/D polymorphism in the control group. The frequency of AA genotype of promoter -866G/A polymorphism was higher obviously in the longevity group than that in the control group, and the frequency of GG and GA genotypes were lower. In 3'UTR-I/D and A55V polymorphisms within UCP2 gene, there was no significant statistic difference of genotypes and alleics distribution between longevity and control groups. Subgroup analysis according to genders showed II genotype of 3'UTR-I/D polymorphism only existed in the male of the longevity group. There was no significantly statistic difference of distribution of every genotype between the same gender in the longevity and control groups. Moreover, the PCR and sequencing of 3'UTR-I/D polymorphism showed that the insertion sequences in Uygur, which was the 45bp repeat sequence were different from that in Pima Indian.There was significant linkage disequilibrium between the each two polymorphisms of -866G/A, A55V and 3'UTR-I/D polymorphisms in the longevity, control groups and all subjects. And in the control group, there was complete linkage disequilibrium between A55V and 3'UTR-I/D polymorphisms. Analysis on 2-polymorphism combinations showed that the frequency of haplotypes D-A of 3'UTR /A55V combination was significantly lower in the longevities than that in the controls. Analysis on the 3-polymorphism combination showed there were no significantly difference of the haplotype on 3-polymorphism combination between longevities and controls.In TaqIB, D442G and I405V polymorphisms within CETP gene, there was no significant difference of genotypes and alleics distribution between longevity and control groups. Subgroup analysis according to genders showed there was only DD genotype in the female of both the longevity and control groups. Every of genotypes of TaqIB and I405V polymorphisms existed in the male and female of both longevity and control groups. There was no significantly statistic difference of distribution of every genotypebetween the same gender in ike longevity and control groups.Linkage disequilibrium analysis showed there was significant linkage disequilibrium between the two polymorphisms of TaqIB and D442G in the longevity, control groups and all subjects, as well as between D442G and I405V. However, there was weak linkage disequilibrium between the two polymorphisms of TaqIB and I405V in the longevity, control groups and all subjects. Haplotype analysis suggested that the frequency of every haplotype had no significantly different in longevity and control groups whether 2 or 3 polymorphisms were brought into the study.ConclusionsAA genotype of promoter-866G/A polymorphism within UCP2 gene was the advantageous factor of longevity. However, D-A haplotype of 3'UTR/A55V polymorphisms was the adverse factor of longevity. And the result of 3'UTR-I/D polymorphism suggested the base sequences of this polymorphism had race specificity. Furthermore, there was the extensive linkage disequilibrium among -866G/A, A55V and 3'UTR, resulted from long-term genetic isolation in Uygur in Xinjiang Hetian.There was no correlation between the alleics, genotypes and haplotypes of polymorphisms within CETP gene, TaqIB, D442G and I405V, and natural longevity of Uygur population in Hetian. But the difference of D442G polymorphism existed in not only races, but also regions where the same race dwelled. Furthermore, there was the extensive linkage disequilibrium between TaqIB and D442G, as well as D442G and I405V, resulted from long-term genetic isolation in Uygur in Xinjiang Hetian.