An NT5E Gene Polymorphism Associates with Low Bone Mineral Density in Chronic Kidney Disease Patients

Arterial calcification is an independent predictor of all-cause and cardiovascular mortality in end-stage renal disease. CD73, a GPI-linked plasma membrane ecto-enzyme encoded by NT5E gene, is involved in vascular calcification inhibition. Mutations in NT5E gene are linked to premature onset of arterial and distal joint calcification in families, possibly due to the downstream effects of CD73 on tissue-non-specific-alkaline-phosphatase (TNAP), an important enzyme in the calcification process. We hypothesised that common single nucleotide polymorphisms (SNPs) in NT5E gene may contribute to the risk of calcifcation in patients with chronic kidney disease (CKD), and explored rs4373339C>T, rs2229523A>G, rs10944128A>G SNPs role on bone mineral density (BMD) and aortic pulse wave velocity (aPWV), the markers of calcification. 302 CKD patients from LACKABO study with calcification markers, haemodynamic and genetic data were studied. The mean age of the CKD cohort was 57.8 ± 15.6 years. rs2229523 SNP showed allele specific differences in BMD, a marker of vascular bone axis; and AA genotype was associated with lower levels of BMD at initial (93.9 versus 125.7 mg/cm3, p = 0.0182) and follow-up (80.4 versus 109.4 mg/cm3, p = 0.0126) screening. These relationships held after adjustments for known confounders of the calcification process. Similar relationship was observed for aPWV with rs2229523 AA genotype. We demonstrated for the first time a non-synonymous variant modulates BMD. These findings offer new insights into the bone-vascular axis in CKD, identifying a novel role for CD73 of potential clinical importance, but further studies are needed to expound the biology driving these observations.