Association of the ENPP1/ENTPD1 Polymorphisms in Hemodialysis Patients

Introduction: ENPP1 and ENTPD1 are two main enzymes involved in ATP-AMP-ADP adenosine axis, which is associated with lipid metabolism, diabetes mellitus (DM) and renal fibrosis. The single nucleotide polymorphisms (SNPs) of ENPP1 and ENTPD1, rs1044498 and rs6584026, are associated with these factors. This retrospective study aimed to address the two SNPs variants in hemodialysis (HD) patients and analyzes their relations with clinical characteristics. Methods: This study included 543 regular HD patients over 3 months at our center. Overnight fasting peripheral blood sample was taken from each subject to extract the DNA. The genotypes of rs1044498 and rs6584026 were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The basic clinical data were noted such as sex, age, and HD-age, and the main causes of chronic kidney disease (CKD) and the clinical characteristics were collected on average at least three times in half a year. T-test and Chi-test were performed for the statistical analyses. Binary logistic regression was applied for the significant parameters by excluding the confounders, gender, age and HD-age. All statistical tests were considered significant for P<0.05. Results: The rs1044498 genotypes showed in two types, A/A and A/C without C/C. The rs6584026 genotypes were C/C and C/T without T/T. The genotype frequency of rs1044498 (A/ C) was 0.238, and the genotype frequency of rs6584026 (C/T) was 0.328. The age and the level of lipoprotein alpha showed statistical significance with rs1044498 variant (A/C, P<0.05). The rs6584026 variant (C/T) was frequently found in patients with nephritis (P<0.05). The albumin, alkaline phosphatase (ALP), lipoprotein alpha, cholesterol, apolipoprotein B (Apo B), Apo B/A1 and nephritis were independently associated with rs6584026 variant (C/T, P<0.05) in binary logistic regression model by controlling the confounders of gender, age and HD-age. High level of triglyceride and low level of urine nitrogen were related to rs6584026 variant (C/T, P<0.05). Conclusion: The rs1044498 and rs6584026 SNPs were related to several high levels of lipids, and rs6584026 variant was related to nephritis and autoimmune disease. The rs6584026 SNP may contribute to the increased risks of cholesterol and ApoB/A1 in HD patients.