| Background:Environmental factor and genetic gene in common effect to decide life-expectancy of mankind. There are many studies about the relation between environmental factor with life-expectancy, but very few known for genetic gene role in life-expectancy. For the past few years, along with study of mankind genomics to have progress, pay close attention to genetics study of longevity. Now focus of scientist study more centralize to relative gene that participate in lipid metabolism, energy metabolism and organism immunoregulation, such as Angiotensin Converting Enzyme gene, Apolipoprotein B gene, Apolipoprotein E gene, cholesterol ester transport protein gene, polymorphism of mitochondria deoxyribonucleic acid, Human Leukocyte Antigen (HLA-DRB, DQB) and tumor necrosis factor (TNF). But the finding of many expert are not unity, show off visible racial diversify.The Uygur nationality centenarian of Xinjiang Hotan district, their population quantity and relative ratio all obviously higher than average level of entire country, so Hotan district is classified as one of longevity region in world by International natural Institute of Medicine. Moreover, because of environment, living characteristic, customs and habits, Uygur who living in this region few to intermarry with outside, there are little population mobility and small genetic drift, medical treatment factoreffect very few, belonging to run its course state, forming a genetic isolates, they are belonging to natural longevity, it is provided very precious and rare resource for us to identity related gene, study the relation between genetic factors with longevity.The study of overseas showed that centenarian longevity correlated with no cardiac and cerebrovascular disease, which frequently occurring illness of aged people, and keep well organism immune state. It is very important to identify longevity gene of mankind that study polymorphisms of ACE, ApoE and HLA-DRB gene, and its relation to natural longevity in Xin Jiang Uygur nationality people.Objective:To explore the interaction of the polymorphism of Apolipoprotein E (ApoE) gene, the distribution of I/D polymorphisms of Angiotensin Converting Enzyme (ACE) gene with Human Leukocyte Antigen (HLA)-DRB gene, and its relation to natural longevity in the Hotan, Xin Jiang Uygur nationality people.Methods:Research objects are Uygur nationality old man of the 7 county, Hotan district in the Xinjiang to carry out epidemiology investigation. Obtained data from 42 cases of centenarians, 102 cases of 90-99 years old group, 70 cases of older group and 53 cases of natural death controls, in the latter two groups ranged in age from 65 to 70 years. Body height and weight, systolic blood pressure and diastolic blood pressure were recorded. Plasma glucose, cholesterol, triglyceride, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, apoprotein A, apoprotein B were measured. Genome DNA was extracted from white blood cells. Using polymerase chain reaction (PCR), polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP),polymerase chain reaction-sequence specific primers (PCR-SSP), single strand conformation polymorphism (SSCP) and direct sequencing technique, we tested ApoE gene, HLA-DRB gene and I/D polymorphisms of ACE gene.Results:No significance deviation from Hardy-Weinberg equilibrium for the polymorphisms in the ApoE gene, HLA-DRB gene and Aï¿¡E gene were observed.The frequencies of ApoE genotypes e 3/4, e 3/3 and e 2/3 were 2.4% > 69%^ 23.8% in the centenarian group, frequencies of the e4> e 3 and e 2 alleles were \.2%^ 82.1% and 16.7%. The frequencies of genotype e 3/4 and e 4> e 3 allele were significantly lower in the centenarian group than controls(P<0.01), the frequencies of genotype e 2/3 and e 2 allele were significantly higher in the centenarian group than controlsThere were positive correlation between the e 2 and longevity, negative correlation with e 4.Moreover, the frequencies of genotype e 2 allele were significantly higher in the centenarian group than older group(P < 0.01). The frequencies of genotype e 3/4 and e 4 allele were significantly lower in the centenarian group than older group(P<0.01).The frequencies of genotype ï¿¡ 2/3 and e 2 allele were significantly higher in the centenarian group than 90-99 years old group(P<0.05). But the frequencies of genotype e 3/4 and e 4 allele no significant difference between the centenarian group with 90-99 years old group. The frequencies of genotype e 3/3 and ï¿¡ 3 allele no significant difference among 4 groups.The frequencies of HLA-DRj and DR6(H) allele were significantly higher in the centenarian group, as compared with that of the controlgroup (9.5% and 1.9%, 9.5% and 0.9%, P <0.05, respectively), while the frequencies of HLA-DR4 and DR9 in the centenarian subjects were 9.5% and 1.2%, significantly lower than that of the control subjects (23.6% and 9.4%, P<0.05, respectively).Moreover, The frequencies of HLA-DR.6(i4) and DR52 allele were significantly higher in the centenarian group, as compared with that of the older group(P<0.05), while the frequency of HLA-DR4, DR9 and DR53 were significantly lower in the centenarian group than older group(P< 0.05, respectively).The frequency of HLA-DRe allele was significantly higher in the centenarian group than 90-99 years old group(P < 0.05), while the frequency of HLA-DR53 was significantly lower in the centenarian group than 90-99 years old group(P < 0.05). The frequencies of the rest genotype no significant difference among 4 groups.The frequencies of ACE genotypes DD> DI and II were 28^/(^ 30.9%> 40.5% in the centenarian group, frequencies of the D and 1 alleles were 0.44 and 0.56. The frequencies of genotype DD and D allele were significantly higher in the centenarian group than controls (P<0.01), same results between centenarian group and older group (P<0.05).The frequencies of genotype DD and D allele no significant difference between the centenarian group with 90-99 years old group. The frequencies of genotypes ID, II and I allele no significant difference among 4 groups.Our data suggest that HLA-DRi and ACE D allele may be an active factor, while the DR9 may be the risk factor for human longevity.Analyses showed no significant difference among 4 groups in BMI, Glu, Triglyceride, cholesterol, SBP and DBP.Conclusion:Our data suggest that HLA-DRi and ACE D allele may be an activefactor, while the DR9 may be the risk factor for human longevity, the interaction of the polymorphism of HLA-DRi with ACE D allele has synergy for longevity.ApoE gene, HLA-DRB gene and I/D polymorphisms of ACE gene have associativity with natural longevity in the Hotan, Xin Jiang Uygur nationality people. This association reflects a genetic influence on differential survival and may point to pleiotropic age-dependent effects on longevity.
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