Relationship Between Klotho Gene Polymorphism And Serum Levels Of Klotho Protein In Patients With Early Renal Damage In Essential Hypertension Patients

Background and ObjectiveEssential hypertension (EH) is a common cardiovascular disease caused by genetic and environmental factor.The disease have a serious impact on human health. The danger of hypertension is the target organ damage,including the kidney damage. The renal damage caused by hypertension have increased recently and hypertension has become one of the main reason for end-stage renal disease (ESRD).Hypertensive patients with early kidney damage have been ignored due to the lack of obvious clinical manifestations and the treatment is delayed,so in-depth to explore the pathogenesis of hypertension of early renal damage is particularly urgent.Klotho gene is closely related to human aging gene found in1997by Kuro-o, and the secreted protein may be an age-related hormone. Animal experiments have showe that the gene Klotho is related to rat kidney damage. The gene is connect with a number of diseases which occur with aging (such as hypertension, coronary heart disease, diabetes, osteoporosis, etc.). This study was designed to investigate the relationship among the Klotho gene G-395A polymorphism, F352V polymorphism, serum Klotho protein level,and serum NO level in hypertension patients with early renal damage. Methods68Essential Hypertension natients,52EH with early renal damage patients and70contral were enrolled into this study.According to the diagnostic criteria of blood pressure (SBP>140mmHg and (or) DBP>90mmHg) from2010China hypertension guidelines.To exclude secondary hypertension,cerebrovascular disease,diabetes,liver and kidney dysfunction,blood diseases,recent infection,long-term use of aspirin and hormones,recent smoking history,urinalysis,blood urea nitrogen (BUN),and creatinine (SCr) are unnormal.Subjects were disabled antihypertensive drugs for two weeks. According to urinary microalbumin (MAU), al-microglobulina (al-MG) and serum ceystatinC (CyS C) as indicators of early renal damage.Divided into hypertensive group (EH-NRD group)52cases and68cases,EH with early renal damage (EH-ERD group),70cases of healthy persons as control group. Application of allele-specific primer PCR (ASP-PCR) detection of Klotho gene G395A point and F352V point polymorphism,enzyme-linked immunosorbent assay determination of serum Klotho protein concentration and serum level of NO.ResultsThe distributions of Klotho G395A Gene Polymorphism in the three groups showed a significant difference (x~2=20.153, P〈0.001).There was a significant difference for the distributions of AA genotype in the EH-NRD group and control (x~2=17.502, P〈0.001).The frequencies ofGallele were61.8%、49.0%and77.1%in three groups.The differences was found between EH-NRD group and control (x~2=7.034, P=0.008).The differences between EH-NRD group and control are also significant (x~2=20.763, P〈O.001)。The distributions of Klotho F352V Gene Polymorphism in the three groups showed a significant difference (x~2=21.633. P〈O.001).The differences was found between the frequency of genotypes in EH patients with or without early renal damage (x~2=18.666, P〈0.001).In the three groups, the differences of frequencies of V allele were significant (P〈O.05)The Klotho protein concentration in the EH patients with or without early renal damage was significantly lower than that of control (P<0.05).The NO concentration in the EH patients with or without early renal damage was significantly lower than that of control (P<0.05).In the three groups, the Klotho protein concentration in GG genotype of Klotho gene were all higher than those in GA genotype and AA genotype (P<0.05),the Klotho protein concentration in FF genotype of Klotho gene were all higher than those in FV genotype and VV genotype (P<0.05).ConclusionThe increase of plasma Klotho protein level might be a protective factor of hypertension and early renal damage caused by hypertension.Klotho gene G-395A polymorphism is associated with EH and EH-ERD patients. AA genetype is liable to hypertension; GG genetype was probably protective for early renal damage. Klotho gene F352V polymorphism is associated with EH and EH-ERD patients. VV genetype is liable to hypertension; FF genetype was probably protective for early renal damage.