Toll-Like Receptor 4 Gene Polymorphism C1196T in Polish Women with Postmenopausal Osteoporosis - Preliminary Investigation.
BACKGROUND
Postmenopausal osteoporosis is a systemic bone disease characterized by low bone mass after menopause. Bone remodeling is regulated by a number of factors, including the immune system. Toll-like receptors 4 (TLR4) are expressed on bone cells and modify the immune response. TLR4 gene polymorphism may take part in the development of chronic inflammation in women after menopause, which is the cause of severe bone resorption.


OBJECTIVE
To examine the frequency of TLR4 C1196T genotypes in postmenopausal osteoporotic and non-osteoporotic Polish women and to investigate the possible relationship between C1196T polymorphism, bone mineral density (BMD) and the incidence of osteoporotic fractures in this group of patients.


METHODS
The study involved 40 postmenopausal women with osteoporosis and 63 healthy postmenopausal non-osteoporotic women. BMD measurements were performed by dual-energy X-ray absorptiometry. DNA was extracted from peripheral blood. Genotyping was performed by real-time PCR using LightSNiP tests with SimpleProbe probes. Melting curve analysis of PCR amplicons enabled the identification of individual C1196T genotypes.


RESULTS
C1196T genotype frequencies in the osteoporotic group were 88% for CC and 12% for CT. In the control group, respectively 86% and 14%. We did not observe the TT genotype. There was no association of C1196T genotypes and BMD nor the incidence of fractures but there was a correlation between genotypes and body height (p=0.035, r=0.415). Homozygous subjects for the C-allele had a lower body height with respect to heterozygous subjects.


CONCLUSIONS
It is unlikely that TLR4 C1196T polymorphism is related to bone mineral density and fracture incidence in Polish osteoporotic women after menopause. However, our data suggests that the C allele may be associated with lower body height in this group. Due to the small number of participants, our observations should be considered as preliminary. Larger studies are needed to confirm our findings.
Department of Clinical Immunology, Transplantation Institute, Medical University of Warsaw, Poland.|Department of Biochemistry and Clinical Chemistry, Medical University of Warsaw, Poland.
Beata
B
Kaleta
Department of Family Medicine, Internal Medicine and Metabolic Bone Diseases, Medical Center of Postgraduate Education, Professor Witold Orłowski Independent Public Clinical Hospital, Warszawa, Poland.
Magdalena
M
Walicka
Department of Family Medicine, Internal Medicine and Metabolic Bone Diseases, Medical Center of Postgraduate Education, Professor Witold Orłowski Independent Public Clinical Hospital, Warszawa, Poland.
Ada
A
Sawicka
Department of Family Medicine, Internal Medicine and Metabolic Bone Diseases, Medical Center of Postgraduate Education, Professor Witold Orłowski Independent Public Clinical Hospital, Warszawa, Poland.
Agata
A
Bogołowska-Stieblich
Department of Clinical Immunology, Transplantation Institute, Medical University of Warsaw, Poland.
Andrzej
A
Górski
Department of Biochemistry and Clinical Chemistry, Medical University of Warsaw, Poland.
Jacek
J
Łukaszkiewicz
Department of Family Medicine, Internal Medicine and Metabolic Bone Diseases, Medical Center of Postgraduate Education, Professor Witold Orłowski Independent Public Clinical Hospital, Warszawa, Poland.
Ewa
E
Marcinowska-Suchowierska
D015502:Absorptiometry, Photon; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D058866:Osteoporotic Fractures / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D010641:Phenotype; D011044:Poland / Q000453:epidemiology; D011110:Polymorphism, Genetic; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D051197:Toll-Like Receptor 4 / Q000235:genetics*
C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4