, 2010,XIV,4; 334-343

Genetic risk markers of low bone mineral density in cystic fibrosis children

Aleksandra Norek1, Dorota Sands2, Agnieszka Sobczyńska-Tomaszewska1, Dariusz Chmielewski3*, Katarzyna Szamotulska4, Kamila Czerska1, Jerzy Bal1


1Zakład Genetyki Medycznej
Kierownik: prof. dr hab. med. T. Mazurczak


2Klinika Pediatrii
Kierownik: dr n. med. B. Radomyska


3Oddział Chirurgii Kręgosłupa i Ortopedii
Kierownik: dr n. med. P. Michalski
*Obecnie: Hospites Lanzarote, Lanzarote, Espana


4Zakład Epidemiologii
Kierownik: dr K. Szamotulska
Instytut Matki i Dziecka, Warszawa
Dyrektor: S. Janus

  • Table I. Clinical and biochemical data in CF patients
  • Table IIa. Genotypes and alleles distribution in the studied polymorphic sites of the COLIA1 gene in patient and control group
  • Table IIb. Genotypes and alleles distribution in the studied polymorphic sites of the VDR gene in patient and control group
  • Table IIc. Genotypes and alleles distribution in the studied polymorphic sites of the CALCR gene in patient and control group
  • Table III. Comparison of Z-score values for particular genotypes of L447P polymorphism in CALCR gene

The aim of the study was verification of the hypothesis concerning the association between polymorphic variants of the following genes: COLIA1, VDR and CALCR considered to be risk factors of bone metabolism disturbances and decreased bone mineral density (BMD) in children with cystic fibrosis (CF).

Material and methods: Clinical evaluation of CF phenotype progression in 101  patients was assessed according to the Shwachman-Kulczycki score. In the project the best value of forced expiratory volume of one second (FEV1) from the six months before densitometric measurements was used. Evaluation of bone tissue condition parameters was always correlated with the analysis of calcium-phosphate metabolism and bone turnover parameters. Densitometric measurements of L1-L4 lumbar spine were made using Lunar DPX IQ 2898. Age and sex of examined persons were standardizated in respect to clinical and biochemical parameters. Molecular analysis was performed in CF patients with the following genotypes: F508del/F508del – 55 persons, F508del/m – 37 persons, m/m – 9 persons. In this project 102 persons formed the control group. Presence of polymorphisms in studied genes was compared with bone tissue parameters.

Results: Low bone mineral density (Z-score<-1 SD) was observed in 53.5% patients and in 26.7% of them BMD was below -2 SD. Patients with low BMD had worse BMI, FEV1 and more severe symptoms of CF. Allele T (BalI) in COLIA1 and allele C (L447P) in CALCR were found to be more frequent in CF patients than in the control group. Allele C in CALCR gene was associated with reduced bone mass. No significant correlation was found between COLIA1 and VDR polymorphisms and BMD.

Conclusions: Process of bone loss in CF patients starts in early childhood and recurrent respiratory infection, malnutrition and corticosteroid therapy are the main factors disturbing metabolic balance of bone tissue. There is a correlation between bone mass loss in CF patients and the appearance of defined gene alleles of bone metabolism. However, we have to emphasize that this type of study needs confirmation on larger groups of patients.

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