title: The melatonin receptor 1A (MTNR1A) gene is associated with recurrent and idiopathic calcium nephrolithiasis.
abstract: BACKGROUND
  Experimental evidence indicate that melatonin regulates some renal tubular functions via specific melatonin receptors (MTNRs) located in the kidney of several avian and mammalian species, including humans. We hypothesized that single nucleotide polymorphisms (SNPs) in the melatonin receptor 1A gene (MTNR1A) might influence the risk of calcium nephrolithiasis.
  
  
  METHODS
  We performed a systematic analysis of the MTNR1A gene in 246 recurrent calcium stone formers (136 men, 110 women; mean age 40.2 ± 12.0 years; body mass index 25.8 ± 4.5 kg/m2) and 269 healthy controls comparable for age and gender without a history of nephrolithiasis.
  
  
  RESULTS
  Two SNPs in Intron 1 of MTNR1A were significantly associated with calcium nephrolithiasis: rs13140012 (P = 0.0004) and rs6553010 (P = 0.009). The haplotypes resulting from the two SNPs were also differently distributed between stone formers and controls, the haplotype A-T being more represented among stone formers (P = 0.00001) and the haplotype T-C being more common in healthy controls (P = 0.00001). Preliminary functional studies showed that the SNP rs13140012 could modify the binding sites for transcription factors.
  
  
  CONCLUSIONS
  The results of this case-control study indicate a strong association between allelic variants of MTNR1A and recurrent calcium nephrolithiasis.
authors.affiliation: Institute of Genetics and Biophysics, Italian National Research Council, Naples, Italy. teresa.esposito@igb.cnr.it
authors.forename: Teresa
authors.initials: T
authors.lastname: Esposito
authors.forename: Domenico
authors.initials: D
authors.lastname: Rendina
authors.forename: Andrea
authors.initials: A
authors.lastname: Aloia
authors.forename: Daniela
authors.initials: D
authors.lastname: Formicola
authors.forename: Sara
authors.initials: S
authors.lastname: Magliocca
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: De Filippo
authors.forename: Riccardo
authors.initials: R
authors.lastname: Muscariello
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mossetti
authors.forename: Fernando
authors.initials: F
authors.lastname: Gianfrancesco
authors.forename: Pasquale
authors.initials: P
authors.lastname: Strazzullo
mesh_terms: D000328:Adult; D001483:Base Sequence; D015415:Biomarkers / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D006801:Humans; D007669:Kidney Calculi / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D053040:Nephrolithiasis / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D044122:Receptor, Melatonin, MT1 / Q000235:genetics*; D012008:Recurrence
chemical_list: D015415:Biomarkers; D044122:Receptor, Melatonin, MT1; D004247:DNA; D002118:Calcium