Research On Kidney Aging And Its Associated Gene Among Uygur People In Hotan, Xinjiang

Objective:To study the relationship between the kidney function decline and the central aortic pressure (CAP) as well as the carotid artery intima-media thickness (CIMT), explore the influence of large blood vessels aging on the kidney function decline and analyze the association of polymorphisms and haplotypes of the klotho and p66shc genes, the candidate genes of kidney aging, with natural longevity and renal decline in Xinjiang Uygur population. Methods:A cross-sectional survey was carried out among 638 clinically healthy Uighur inhabitants enrolled in Hotan, Xinjiang, including 291 males and 347 females aged from 18 to 95 years old, with their blood pressure, serum creatinine and others being measured, calculating the eGFR (estimated glomerular filtration rate) using the formula of MDRD based Chinese, measuring the CAP [systolic blood pressure mainly centers (C-SBP), central pulse pressure (C-PP), increased pressure (AP), augmentation index (AIX) and other components] with the PWA from Australia and CIMT with carotid ultrasonography. The relationships of renal function aging with the CAP and CIMT were explored using Multivariate analysis. Through a Case-control method and Snapshot genotyping method, studies were made on the distributions of polymorphisms and haplotypes in the Klotho gene at rs9527025, rs9536314, rs1207568 and rs564481 gene loci, and in the P66shc gene at rs8191981 and rs4845401 gene loci among clinically healthy Uygur volunteers without any blood relation with the long-lived group and with no family history of longevity being the control and people older than ninety as the long-lived group in Hotan of Xinjiang and on the association of their variations with the longevity and renal function aging among long-lived people. Results: 1) There were gender differences in aging-related changes in the renal function, AP and AIX:AP and AIX increased more evidently among females in each age group; 2) The people with higher AIX were elder and with more evidently declined renal function and increased C-PP and AP than with lower AIX; 3) Multivariate analysis results showed that eGFR was negatively correlated with the AIX, and unrelated with the brachial artery pressure; 4). The eGFR was negatively correlated with the CIMT, however, significantly uncorrelated after adjustment for age, gender, body mass index, blood pressure, lipids and other factors (P>0.05); 5) The genotype and allele frequency distributions of P66shc gene and Klotho gene were consistent with Hardy-Weinberg equilibrium testing (P> 0.05); 6) There was no statistical difference of the focus genotype and allele frequency distributions in Klotho and P66shc genes between the control and long-lived group; 7) the detected gene loci mutation in Klotho and P66shc genes focus was not statistically related with the longevity of Uygur through correlation analysis (P>0.05); 8) There was no statistical difference of Klotho and P66shc genotype, allele and haplotypes frequency distributions between two groups of the normal renal function (eGFR≥90 (ml/min/1.73m2) and the renal dysfunction (eGFR<90 (ml/min/1.73m2) in the longevity group, divided by the decline of renal function (P>0.05); 9) The Klotho and P66shc gene polymorphisms were not statistically correlated with the renal decline of long-lived Uygurs in a correlation analysis; 10) The combined effect of polymorphism of P66shc gene at rs8191981 and klotho gene at rs9536314 was statistically correlated with renal function decline among long-lived Urgurs, showed in a analysis of interaction of P66shc and klotho genes on the renal function decline of the long-lived people (R=0.082, P=0.008). Conclusion:The study among the healthy Uygur adults showed that central aortic pressure, a function indicator for early atherosclerosis, was related to the renal function physiological decline, after adjustment for age, gender, and etc. And CIMT, a structural indicator for early atherosclerosis, was not significantly related to the aged-related renal function decline. No evidence showed in the two groups that the polymorphisms of P66shc and klotho genes were vulnerable genetic factors for the longevity and renal decline of the long-lived Uygurs in Hotan. The combined effect of polymorphism of P66shc gene at rs8191981 and Klotho gene at rs9536314 was correlated with renal function decline among long-lived Urgurs.