Association between KLOTHO Gene G395A Polymorphism and Carotid Artery Calcification in regular Hemodialysis Patients

Abstract

BACKGROUND: The vascular calcification process in chronic kidney disease (CKD) is a complication caused by mineral and bone abnormalities and becomes the risk of cardiovascular disease and mortality in CKD patients. KLOTHO is an inhibitor of calcification and its expression has been observed to decrease in CKD patients. The KLOTHO gene G395A polymorphism is a genetic variation that is common in Asian populations and is associated with vascular dysfunction in hemodialysis patients.
 OBJECTIVE: The objective of the study was to determine the association between the KLOTHO gene G395A polymorphism and carotid artery calcification in regular hemodialysis patients.
 METHODS: This study was an analytical study with a cross-sectional design and was carried out at Rasyida Kidney Hospital Medan. Venous blood sample was taken from the patients who met the inclusion criteria for examination of the KLOTHO gene -395 polymorphism and carotid ultrasonography was assessed to evaluate the thickness of the tunica media-intima as a marker of vascular calcification.
 RESULTS: The majority of the study subjects were men, as many as 35 patients (50.7%). From the results of the KLOTHO gene -395 polymorphism, it was found that the majority of subjects had GG genotypes as many as 36 people (52.2%) followed by GA genotypes as many as 30 people (43,5%) and AA genotypes as many as 3 (4,3%). There was a statistically significant of the association between KLOTHO gene -395 polymorphism and the incidence of carotid artery calcification (p = 0,015).
 CONCLUSION: There was an association between the KLOTHO gene G395A polymorphism and carotid artery calcification in regular hemodialysis patients.

The Role of Klotho G395A Gene Polymorphism in Atherosclerotic Cardiovascular Disease and Mortality Risk Scores in Non-dialysis Chronic Kidney Disease

“…( 16) In Indonesia, a prior investigation on the klotho G395A SNP in the Medan population revealed that the majority of participants (52.2%) had the GG genotype, followed by the GA genotype (43.5%), and the AA genotype (4.3%). (10) There was a link between the klotho G395A SNP and the occurrence of carotid artery calcification. (10) Conflicting finding was noted regarding the effect of G/A substitution on the expression of G395A in the promoter of the klotho gene.…”

“…(10) There was a link between the klotho G395A SNP and the occurrence of carotid artery calcification. (10) Conflicting finding was noted regarding the effect of G/A substitution on the expression of G395A in the promoter of the klotho gene. Nevertheless, the A allele had been reported to form fewer DNA-protein complexes compared to the G allele.…”

“…More than 10 SNPs have been identified in the human klotho gene, including the G395A SNP in the promoter region of the klotho gene. (9) G395A SNP is the most common variation of klotho gene in Asian populations (10) and is associated with CVD (11). This SNP may affect klotho expression, in which klotho deficiency has been linked to the increased risk of hypertension, CAD, and metabolic syndrome.…”