The Study Of The Association Between Telomerase Gene Polymorphisms And Susceptibility To Chronic Kidney Disease

BackgroundToday,Chronic Kidney Disease(CKD)has gradually developed into a high-risk disease and has become a major disease that threatens human health after cancer,cardiovascular disease and diabetes around the world.Due to its increasing incidence and prevalence each year,CKD has become one of the major public health concerns in recent decades.So far,there have been more than 600 million patients with CKD worldwide,and more than one million of them die each year.With a large population in China,the total number of patients with CKD is huge.Because of the lack of good therapeutic drugs and radical cures,the treatment cost is high and it may cause serious cardiovascular complications.Chronic kidney disease not only imposes a heavy burden on patients and their families,but also has a huge impact on society and economy.In addition,with the gradual progression of CKD,the patient's kidney function will be gradually impaired,eventually leading to kidney failure.Therefore,early diagnosis and early treatment are particularly important for CKD.Primary glomerulonephritis(GN)is a major cause of CKD and often develops End Stage Renal Disease(ESRD),but the underlying causes are not fully understood.Studies have shown that shorter leukocyte telomere length(LTL)is associated with susceptibility to CKD and reduced renal function.However,it is not clear whether telomerase gene polymorphisms are related to increased risk of GN?CKD and ESRD.ObjectivesThe purpose of this study was to investigate whether CKD has a correlation with rs2736100,a genetic polymorphism site in the Telomerase Reverse Transcriptase(TERT),and rs 12696304,a genetic polymorphism site in Telomerase RNA Component(TERC),providing a scientific basis for the study of etiology and early prediction and diagnosis of CKD.In addition,we also focus on whether telomere length can affect the incidence of CKD and disease progression.MethodsIn this study,a case-control study was performed.The case group includes 769 specimens from patients with CKD(243 cases of non-end stage renal disease and 526 cases of end stage disease),all of which were derived from primary glomerulonephritis.Normal control group includes 515 healthy individuals without kidney-related diseases.The age and gender of the subjects in the experimental group and the control group had matched with each other.Peripheral blood samples of all subjects were collected and peripheral blood leukocyte genomic DNA was extracted thereafter.The Taq-Man probes were used to detect the genetic polymorphisms of rs12696304 and rs2736100.In addition,the Q-PCR was used to measure the telomere length of all samples.Results1.Among 769 cases of chronic kidney disease,243 cases of non-end stage renal disease and 526 cases of end stage renal disease were included.The mean age of non-end stage renal disease specimens was 43 ± 14 years old,including 133 male specimens and 110 female specimens.The mean age of end stage renal disease specimens was 46 ± 11 years old,including 301 males and 225 females.A total of 515 normal controls were collected,with an mean age 46 ± 12 years,including 289 males and 226 females.2.By grouping the age of onset of patients,it was found that the number of patients with chronic kidney disease was mainly concentrated between 40 and 50 years of age.3.The frequency distributions in the control and cases groups were all consistent with Hardy-Weinberg's law of genetic equilibrium.4.Allele G and genotype GG at rs12696304 are at increased risk for chronic kidney disease(GG vs.CC:OR = 1.557,95%CI = 1.052-2.306,P = 0.026;GG vs.CC +CG:OR = 1.465,95%CI = 1.170-1.834,P = 0.001;G vs.C:OR = 1.334,95%CI =1.122-1.586,P = 0.001),but this risk is only relevant to the females.5.The rs2736100 gene polymorphism was not associated with the risk of chronic kidney disease.However,in the ESRD female subgroup,the frequency of rs2736100 allele C and genotype CC was significantly higher than that of the corresponding control group.6.In the control group and the CKD group,the relative telomere length decreased with age,but there was no difference in relative telomere length between the two groups,indicating that the telomere homeostasis was not seriously impaired.Therefore,the association between the allele G at rs12696304 and the increased risk of primary glomerulonephritis cannot be attributed to the regulation of telomere length.