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


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.
Corbetta
S
S
Endocrinology and Diabetology Unit, Department of Medical-Surgical Sciences, University of Milan, IRCCS Policlinico San Donato, 20097 San Donato Milanese, Milan, Italy. sabrina.corbetta@unimi.it
Eller-Vainicher
C
C
Frigerio
M
M
Valaperta
R
R
Costa
E
E
Vicentini
L
L
Baccarelli
A
A
Beck-Peccoz
P
P
Spada
A
A
D000368:Aged; D002712:Chlorides / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000453:epidemiology* / Q000235:genetics*; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D007669:Kidney Calculi / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D010070:Oxalates / Q000378:metabolism; D011110:Polymorphism, Genetic; D015995:Prevalence; D012307:Risk Factors; D000076988:Sulfate Transporters
D002712:Chlorides; D026901:Membrane Transport Proteins; D010070:Oxalates; C439529:SLC26A6 protein, human; D000076988:Sulfate Transporters