| BackgroudAging is a universal biological reality that is familiar to everyone. The definition proposed by Robert Arking is one of the most global and rigorous descriptions of the aging process:"the time-independent series of cumulative, intrinsic, and deleterious functional and structural changes that usually begin to manifest themselves at reproductive maturity and eventually culminate in death."If not, slow down the aging process, achieving old age.Aging 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 disease.ObjectivesTo investigate the association between polymorphisms (5178A/C and 10398G/A) and their haplotype within mitochondrial DNA (mtDNA), as well as polymorphism 825 C/T of GNB3 gene and natural longevity in Xinjiang Uygur population.MethodsWe conducted a case-control study consisting of 165 natural longevity cases (including 65 centenarians and 100 people aged 90-99) and 112 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 blood pressure (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 5178A/C and 10398G/A within mtDNA and 825C/T within GNB3 gene, and performed the linkage disequilibrium and haplotype analysis.ResultsThe study about mtDNA polymorphisms showed the distribution frequency of the 5178A in the centenarian is slightly higher than in those of controls . The frequency of the 10398G were significantly higher among the centenarian and longevity in comparison to the controls. The frequency of AA genotype of 5178A/C polymorphism was higher obviously in the centenarian and longevity group than that in the control group, and the frequency of GG genotypes of 10398G/A polymorphism was higher obviously in the centenarian group than that in the control group. In 5178A/C and 10398G/A polymorphisms within mtDNA, there was no significant statistic difference of genotypes and allelics distribution between centenarian and longevity groups. There was no significantly statistic difference of distribution of every genotype between the same gender in the centenarian, longevity and control groups.Analysis on 2-polymorphism combinations showed that the frequency of A-G genotypes combination of 5178/10398(A-G haplotype) was significantly higher in the centenarian and longevity groups than that in the controls.In 825C/T polymorphisms within GNB3 gene, there was no significant difference of genotypes and allelics distribution between centenarian and longevity groups. The frequency of C/T polymorphism and alleles of the centenarians and longevity group were significantly different from that of the controls. The frequency rate of C/C genotype of the centenarians was significantly higher than of the controls . This significance also found between old-age groups and controls. No significant differences were found between centenarians and old–age groups for genotypes and allele frequency distribution. There was no significantly statistic difference of distribution of every genotype between the same gender in the centenarian, longevity and control groups.ConclusionsAA genotype of 5178A/C polymorphism within mtDNA and GG genotype of 10398G/A polymorphism within mtDNA were the advantageous factor of longevity. However, CC genotype of 5178A/C polymorphism within mtDNA and AA genotype of 10398G/A polymorphism within mtDNA were the adverse factor of longevity. Furthermore, A-G genotypes combination(A-G haplotype) of 5178/10398 polymorphisms were the advantegeous factor of longevity, resulted from long-term genetic isolation in Uygur in Xinjiang Hetian.There was correlation between the allelics and genotypes of polymorphisms within GNB3 gene 825C/T and natural longevity of Uygur population in Hetian. But no significant differences were found between centenarians and old–age groups for genotypes and allele frequency distribution. Our study suggest that GNB3 gene C825T polymorphism is closely correlated with life span of individuals in Xinjiang Hotan Uiygur population. |
