Literature DB >> 24783428

The importance of 8993C>T (Thr399Ile) TLR4 polymorphism in etiology of osteoporosis in postmenopausal women.

Izabela Uzar, Przemyslaw M Mrozikiewicz, Anna Bogacz, Joanna Bartkowiak-Wieczorek, Hubert Wolski, Agnieszka Seremak-Mrozikiewicz, Krzysztof Drews, Witold Kraśnik, Adam Kamiński, Bogusław Czerny.   

Abstract

INTRODUCTION: 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.
MATERIAL AND 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.

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Year:  2014        PMID: 24783428     DOI: 10.17772/gp/1710

Source DB:  PubMed          Journal:  Ginekol Pol        ISSN: 0017-0011            Impact factor:   1.232


  2 in total

Review 1.  The transforming growth factor-β1 (TGF-β1) gene polymorphisms (TGF-β1 T869C and TGF-β1 T29C) and susceptibility to postmenopausal osteoporosis: a meta-analysis.

Authors:  Jiajia Sun; Chi Zhang; Lei Xu; Mingyuan Yang; Huilin Yang
Journal:  Medicine (Baltimore)       Date:  2015-01       Impact factor: 1.889

2.  TLR4 Inactivation in Myeloid Cells Accelerates Bone Healing of a Calvarial Defect Model in Mice.

Authors:  Dan Wang; James R Gilbert; Gwen M Taylor; Chhinder P Sodhi; David J Hackam; Joseph E Losee; Timothy R Billiar; Gregory M Cooper
Journal:  Plast Reconstr Surg       Date:  2017-08       Impact factor: 4.730

  2 in total

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