The importance of 8993C>T (Thr399Ile) TLR4 polymorphism in etiology of osteoporosis in postmenopausal women.
BACKGROUND
Toll-like receptors (TLR) may play a key role in initiating cellular signaling pathways by increasing the levels of inflammatory cytokines which, cooperating with osteoclasts, influence bone turnover Numerous research articles focused on the genetic background of this condition, among others on polymorphic variants in TLR genes. The aim of the study was to examine the role of 20877G>A (Arg753GIn) in TLR2 gene and 8993C>T (Thr399lle) in TLR4 gene in the etiopathogenesis of postmenopausal osteoporosis in Polish women.


METHODS
This study included 180 postmenopausal women (t-score < or = -2.5), 153 postmenopausal women with osteopenia (t-score between -2.5 and -1), and 91 postmenopausal healthy women with correct t-score (t-score >-1). The 20877G>A TLR2 and 8993C>T TLR4 polymorphisms were determined by PCR/RFLP analysis.


RESULTS
The analysis did not reveal statistically significant differences in the distribution of genetic variants of 20877G>A TLR2 polymorphism between the investigated groups of women. The most interesting results were connected with 8993C>T TLR4 polymorphism. Comparison of the group with osteoporosis and controls revealed overrepresentation of heterozygous 8993CT genotype (13.3 vs. 5.5%, OR=2.65, p=0.03). Also, mutated 8993T allele was overrepresented in the group with osteoporosis (6.7 vs. 2.7%, OR=2.52, p=0.04). Higher frequency of heterozygous 8993CT genotype (13.3 vs. 4.6%, OR=3.21, p=0.004) and mutated 8993T allele (6.7 vs. 2.3%, OR=3.05, p=0. 005) was noted in osteoporotic women as compared to the group with osteopenia. Higher frequency of heterozygous 8993CT genotype (13.3% vs. 5.3%, OR=2.73, p=0.003) and mutated 8993T allele (6.7 vs. 2.7%, OR=2.67, p=0.004) was observed in the group with osteoporosis as compared to women with osteopenia and with correct t-score.


CONCLUSIONS
Results of our study suggest an important role of mutated 8993T allele of 8993C>T TLR4 polymorphisms in the etiology of postmenopausal osteoporosis. Nevertheless, this observation requires further investigation with larger sample size comprised of Polish women.
Izabela
I
Uzar
Przemyslaw M
PM
Mrozikiewicz
Anna
A
Bogacz
Joanna
J
Bartkowiak-Wieczorek
Hubert
H
Wolski
Agnieszka
A
Seremak-Mrozikiewicz
Krzysztof
K
Drews
Witold
W
Kraśnik
Adam
A
Kamiński
Bogusław
B
Czerny
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000235:genetics; D001851:Bone Diseases, Metabolic / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D015663:Osteoporosis, Postmenopausal / Q000235:genetics* / Q000473:pathology*; D011044:Poland; D011110:Polymorphism, Genetic; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D044465:White People / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4