Genetic Polymorphisms in Calcitonin Receptor Gene and Risk for Recurrent Kidney Calcium Stone Disease

Abstract

<b><i>Introduction:</i></b> In this study the full sequence of the calcitonin receptor gene <i>(CALCR)</i> in a group of Iranian males suffering from recurrent calcium urinary stones was compared with that of a control group. <b><i>Methods:</i></b> Serum and urinary biochemistry related to urolithiasis were evaluated in 105 males diagnosed with recurrent kidney calcium stones and 101 age-matched healthy control males. The polymerase chain reaction single-strand conformation polymorphism method was used to detect new polymorphisms in the <i>CALCR</i>. <b><i>Results:</i></b> Nine polymorphisms were detected; seven were in the non-coding and two in the coding region. The T allele associated with the <i>3</i>′<i>UTR+18C>T</i> polymorphism was observed exclusively in the stone formers. The exact odds ratio for the T allele in this locus for those at risk of stone formation was 36.72 (95% CI 4.95-272.0) (p < 0.001). The mean (standard deviation) urine calcium concentration was 117 (60) mg/l in patients with the C allele and 152 (72) mg/l in those with the T allele (p = 0.03). In addition, <i>IVS1-6T>C</i> and <i>IVS1insA</i> polymorphisms in intron 1 were associated with kidney stone disease (p < 0.001). Regarding single nucleotide polymorphism 447, mean (standard deviation) of serum calcitonin levels were 16.7 (18.7) pg/ml, 10.5 (11.0) pg/ml and 9.94 (9.7) pg/ml in subjects with TT, TC and CC genotypes, respectively (p = 0.01). <b><i>Conclusion:</i></b> Our data indicate a potential association between <i>3</i>′<i>UTR+18C>T</i> and intron 1 polymorphisms in the <i>CALCR</i> and the risk of kidney stone disease.