title: The relationship of 3' vitamin D receptor haplotypes to urinary supersaturation of calcium oxalate salts and to age at onset and familial prevalence of nephrolithiasis.
abstract: BACKGROUND
  Idiopathic hypercalciuria (IHc) and idiopathic hypocitraturia are frequently associated with calcium nephrolithiasis. We investigated the relationship of vitamin D receptor (VDR) polymorphisms (BsmI, TaqI and FokI) to urinary supersaturation of calcium oxalate salts in recurrent calcium oxalate stone formers with IHc and the clinical relevance of this relationship.
  
  
  METHODS
  The study included 110 Caucasian stone formers with IHc and 127 unrelated healthy controls without history of nephrolithiasis. Age at onset of nephrolithiasis, familial history score (FHS) and the ion activity product of calcium oxalate salts in urine (AP(CaOx)) were tabulated. BsmI, TaqI and FokI VDR polymorphisms were evaluated in all participants.
  
  
  RESULTS
  Patients and controls were classified as homozygous (bbTT and BBtt) or heterozygous in relation to BsmI and TaqI polymorphisms. Compared with BBtt patients, bbTT homozygous stone formers showed lower citrate excretion (1.91+/-0.89 vs 3.46+/-1.39 mmol/24 h, P = 0.004) and higher AP(CaOx) (2.02+/-0.51 vs 1.53+/-0.53, P = 0.006). Among controls, there were similar differences in citrate excretion and AP(CaOx) between the two groups, but they were not statistically significant. Compared with BBtt, bbTT patients showed lower mean age at onset of nephrolithiasis (29.7+/-12.1 vs 38.1+/-12.7 years, P = 0.008) and higher values of FHS (2.45+/-1.9 vs 0.83+/-0.7, P = 0.006). Similar results were obtained for individual BsmI and TaqI alleles. The analysis of FokI alleles was not informative.
  
  
  CONCLUSIONS
  Recurrent calcium oxalate stone formers with IHc and the bT VDR haplotype have more aggressive kidney stone diseases as indicated by a higher familial incidence and lower mean age at onset. This clinical severity is associated with the higher urinary supersaturation of calcium oxalate salts and abnormalities of renal citrate handling.
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, Università Federico II, via S. Pansini 5, 80131 Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mossetti
authors.forename: Domenico
authors.initials: D
authors.lastname: Rendina
authors.forename: Roberto
authors.initials: R
authors.lastname: Viceconti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Manno
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Guadagno
authors.forename: Pasquale
authors.initials: P
authors.lastname: Strazzullo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Nunziata
mesh_terms: D000328:Adult; D017668:Age of Onset; D002129:Calcium Oxalate / Q000378:metabolism* / Q000652:urine; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D007674:Kidney Diseases / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D020347:Lithiasis / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D015995:Prevalence; D018167:Receptors, Calcitriol / Q000235:genetics*
chemical_list: D018167:Receptors, Calcitriol; D002129:Calcium Oxalate