The impact of an URAT1 polymorphism on the losartan treatment of hypertension and hyperuricemia

J Clin Lab Anal. 2021 Oct;35(10):e23949. doi: 10.1002/jcla.23949. Epub 2021 Sep 8.

Abstract

Background: This study was designed to evaluate the impact of polymorphisms in the urate transporter 1 (URAT1) gene on the uricosuric action of losartan therapy in hypertensive patients suffering from hyperuricemia.

Methods: A MassARRAY approach was used to detect single nucleotide polymorphism (SNP) loci in the URAT1 and CYP2C9 genes (16 and 2 loci, respectively) in 111 patients with hypertension and hyperuricemia taking losartan and in 121 healthy controls. In addition, we compared serum urate (SUA) levels and other key clinical biochemistry indices between these two patient groups.

Results: We detected significant differences between the two patient groups with respect to age, SUA, urea, creatine, triglycerides, high-density lipoprotein, low-density lipoprotein, and fasting plasma glucose (all p < 0.05). In addition, we found that hypertensive patients with hyperuricemia were more likely to exhibit the rs3825016(C/T) (36.9% vs 21.5%, p = 0.03), and we determined that a 2-week treatment course with losartan was associated with significant decreases in SUA values (p < 0.001).

Conclusion: Our findings indicate that the URAT1 rs3825016 polymorphism may influence the uricosuric action of losartan.

Keywords: CYP2C9; URAT1; hypertension with hyperuricemia; losartan.

MeSH terms

  • Adult
  • Aged
  • Antihypertensive Agents / therapeutic use*
  • Cytochrome P-450 CYP2C9
  • Female
  • Humans
  • Hypertension* / drug therapy
  • Hypertension* / epidemiology
  • Hypertension* / genetics
  • Hyperuricemia* / drug therapy
  • Hyperuricemia* / epidemiology
  • Hyperuricemia* / genetics
  • Losartan / therapeutic use*
  • Male
  • Middle Aged
  • Organic Anion Transporters / genetics*
  • Organic Cation Transport Proteins / genetics*
  • Pharmacogenomic Testing
  • Pharmacogenomic Variants / genetics
  • Polymorphism, Single Nucleotide / genetics

Substances

  • Antihypertensive Agents
  • Organic Anion Transporters
  • Organic Cation Transport Proteins
  • SLC22A12 protein, human
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Losartan