Analysis of the 206M polymorphic variant of the SLC26A6 gene encoding a Cl- oxalate transporter in patients with primary hyperparathyroidism

Eur J Endocrinol. 2009 Feb;160(2):283-8. doi: 10.1530/EJE-08-0623. Epub 2008 Nov 24.

Abstract

Objective: Primary hyperparathyroidism (PHPT) is often complicated by kidney stones. Hypercalciuria and urine oxalate excretion are considered risk factors for urolithiasis in PHPT as well as in idiopathic stone-formers. Recently, the anion-exchanger SLC26A6 has been involved in the oxalate metabolism.

Design and methods: We tested the hypothesis that the 206M polymorphic variant of SLC26A6 gene might contribute to the risk of kidney stones in PHPT. DNA samples from 145 PHPT patients and 129 age- and sex-matched healthy subjects were genotyped.

Results: The homozygous 206V genotype was the most frequent both in PHPT patients and controls (79.3 and 74.4%), while heterozygosity for the 206M allele was detected in 20.0 and 23.3% respectively. The homozygous 206M genotype was extremely rare, occurring in 0.7 and 2.3% of PHPT and healthy subjects respectively. In the PHPT cohort, the prevalence of urolithiasis did not differ between the V/V and V/M+M/M groups and urine oxalate excretions did not correlate with the genotype. Considering the subset of PHPT stone formers (n=74), calciuria was lower in V/M+M/M patients with respect to V/V stone-formers (4.40+/-1.88 vs 5.92+/-2.62 mg/kg per 24 h; mean+/-s.d., P=0.034). Finally, the SLC26A6 206M alleles were significantly related to the presence of hypertension (73.3 vs 47.8%), showing an OR of 4.8.

Conclusions: Though the SLC26A6 206M polymorphism did not correlate with kidney stone development in PHPT patients, PHPT stone-formers harbouring the M allele had a lower hypercalciuria. This observation and the high prevalence of hypertension associated with the 206M polymorphism need further investigation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Chlorides / metabolism
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / epidemiology
  • Genotype
  • Humans
  • Hyperparathyroidism, Primary / epidemiology*
  • Hyperparathyroidism, Primary / genetics*
  • Incidence
  • Italy / epidemiology
  • Kidney Calculi / epidemiology*
  • Kidney Calculi / genetics*
  • Male
  • Membrane Transport Proteins / genetics*
  • Membrane Transport Proteins / metabolism
  • Middle Aged
  • Oxalates / metabolism
  • Polymorphism, Genetic
  • Prevalence
  • Risk Factors
  • Sulfate Transporters

Substances

  • Chlorides
  • Membrane Transport Proteins
  • Oxalates
  • SLC26A6 protein, human
  • Sulfate Transporters