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

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/MCM/M groups and urine oxalate excretions did not correlate with the genotype. Considering the subset of PHPT stone formers (nZ74), calciuria was lower in V/MCM/M patients with respect to V/V stone-formers (4.40G1.88 vs 5.92G2.62 mg/kg per 24 h; meanGS.D., PZ0.034). 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.

Estimated glomerular filtration rate by serum cystatin C correlates with cardiometabolic parameters in patients with primary hyperparathyroidism

“…PHPT has been recognized as a risk factor for impaired renal function, though the specific relationship between PHPT and this condition is not completely understood. Recent studies demonstrated that prolonged activation of the intrarenal inflammosome is responsible for the loss of kidney function in oxalate crystal nephropathy (15), which frequently occurs in PHPT (16,17).…”

MECHANISMS IN ENDOCRINOLOGY: Kidney involvement in patients with primary hyperparathyroidism: an update on clinical and molecular aspects

“…SLC26A6, the gene coding for a sulphate transporter, is expressed in the human distal segments of the proximal tubules where it mediates oxalatedependent NaCl absorption. The 206M polymorphic variant of the SLC26A6 gene, whose encoded protein exhibits reduced activity, is not associated with kidney stones in PHPT patients, though it has been shown to be associated with less severe hypercalciuria in PHPT patients with stone formation, suggesting a role of SCL26A6 as contributor in kidney stone development in PHPT patients (35).…”

Analysis of candidate genes of QTL and chromosomal regions for essential hypertension in the rat model

“…Only one candidate gene is associated with hypertension in human populations. In a study of the 206 M polymorphic variant of the SLC26A6 gene encoding a Cl(-)-oxalate transporter in patients with primary hyperparathyroidism, Corbetta et al [65] found that the SLC26A6 206M alleles were significantly related to the presence of hypertension.…”