title: Fok-I polymorphism of vitamin D receptor gene and the presence of renal dysfunction in patients with β-thalassemia major.
abstract: Recent evidence supports the presence of renal dysfunction even among young patients with β-thalassemia major. However, the possible genetic contribution has never been investigated. The aim of this study was to correlate the presence of Fok-I polymorphism of the vitamin D receptor gene with abnormal levels of early markers of renal impairment in children and young adults with thalassemia. Thirty-four patients (19 male and 15 female) with β-thalassemia major on conventional treatment, with a mean decimal age of 14.62 ± 5.47 years (range: 5-22 years), were included in the study. Markers of renal function were determined in serum and in urine and patients were genotyped for Fok-I gene polymorphism. Genotype frequencies were similar to those previously reported for other populations: 47.06% of the patients were homozygous for the F allele, 41.18% were heterozygous, and 11.76% were homozygous for the f allele. A considerable number of patients demonstrated impaired renal function with increased serum cystatin C levels (29.41%), glomerular dysfunction with proteinuria (68%), as well as significant tubulopathy with hypercalciuria (73.08%), and increased levels of urinary β(2)-microglobulin (29.41%). When patients were stratified according to Fok-I polymorphism, a significantly higher prevalence of abnormally increased serum levels of cystatin C was observed in patients being homozygous for the f allele (75%) compared with those being heterozygous (Ff) or homozygous for the F allele (14.29% and 31.25%, respectively, P = .02). Further studies are needed to confirm these preliminary results and elucidate the possible mechanisms involved.
authors.affiliation: First Paediatric Department, Aristotle University of Thessaloniki, Greece. christoforidis@doctors.org.uk
authors.forename: Meropi
authors.initials: M
authors.lastname: Dimitriadou
authors.forename: Athanasios
authors.initials: A
authors.lastname: Christoforidis
authors.forename: Marina
authors.initials: M
authors.lastname: Economou
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Teli
authors.forename: Nikoleta
authors.initials: N
authors.lastname: Printza
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Tzimouli
authors.forename: Ioanna
authors.initials: I
authors.lastname: Tsatra
authors.forename: Liana
authors.initials: L
authors.lastname: Fidani
authors.forename: Fotis
authors.initials: F
authors.lastname: Papachristou
authors.forename: Miranda
authors.initials: M
authors.lastname: Athanassiou-Metaxa
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002118:Calcium / Q000652:urine; D002648:Child; D002675:Child, Preschool; D055316:Cystatin C / Q000097:blood; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005920:Glomerular Mesangium / Q000378:metabolism; D006801:Humans; D007674:Kidney Diseases / Q000097:blood / Q000235:genetics* / Q000652:urine; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D011507:Proteinuria / Q000097:blood / Q000652:urine; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000652:urine; D017086:beta-Thalassemia / Q000097:blood / Q000235:genetics* / Q000652:urine
chemical_list: D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D018167:Receptors, Calcitriol; D001613:beta 2-Microglobulin; D002118:Calcium