Association of MPPED2 gene variant rs10767873 with kidney function and risk of cardiovascular disease in patients with hypertension

J Hum Genet. 2023 Jun;68(6):393-398. doi: 10.1038/s10038-022-01118-w. Epub 2023 Feb 16.

Abstract

Changes in kidney function and the progression of chronic kidney disease (CKD) are associated with the risk of cardiovascular disease (CVD) and influenced by genetic factors. However, the association between genetic variants and kidney function in patients treated with antihypertensive drugs remains uncertain. This study aimed to examine the association between 30 variants locating at the 22 genes and the risk of kidney function evaluated by the estimated glomerular filtration rate (eGFR) in 1911 patients with hypertension from a Chinese community-based longitudinal cohort (including 1220 participants with CKD and 691 without CKD at baseline). By using multivariate linear regression analysis after adjustment for age, sex, traditional cardiovascular risk factors, and the use of antihypertensive drugs, as well as after correction for multiple comparison, patients with rs10767873T allele of the metallophosphoesterase domain containing 2 (MPPED2) gene were associated with higher level of eGFR (β = 0.041, p = 0.01) and lower levels of serum creatinine (β = -0.068, p = 0.001) and serum uric acid (β = -0.047, p = 0.02). But variant rs10767873 was not found to be associated with the risk of CKD, regardless of the types of antihypertensive drugs used. During a median 2.25-year follow-up, 152 CVD events were documented. Interestingly, patients with the rs10767873TT genotype had an increased risk of CVD events (hazard ratio, 1.74, 95% confidence interval, 1.11 to 2.73; p = 0.02) compared with patients carrying the wild-type genotype of rs10767873CC. In conclusion, our findings suggest variant rs10767873 of the MPPED2 gene is associated with kidney function and risk of CVD in Chinese hypertensive patients.

MeSH terms

  • Antihypertensive Agents / therapeutic use
  • Cardiovascular Diseases* / complications
  • Cardiovascular Diseases* / genetics
  • Glomerular Filtration Rate / genetics
  • Humans
  • Hypertension* / complications
  • Hypertension* / genetics
  • Kidney
  • Phosphoric Diester Hydrolases
  • Renal Insufficiency, Chronic* / complications
  • Renal Insufficiency, Chronic* / genetics
  • Risk Factors
  • Uric Acid

Substances

  • Antihypertensive Agents
  • Uric Acid
  • MPPED2 protein, human
  • Phosphoric Diester Hydrolases