Santos J L, Lera L, Pérez-Bravo F, Albala C
Laboratory of Genetic and Nutrition Epidemiology, Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago, Chile.
Ann Hum Biol. 2006 Sep-Dec;33(5-6):585-92. doi: 10.1080/03014460601011798.
It has been proposed that the toll-like receptor-4 gene (TLR4) may participate in the development of obesity and osteoporosis, in addition to its well-known role in the immune response. On the other hand, the adipose tissue of obese subjects shows an increased expression of the proinflammatory cytokine, tumour necrosis factor-alpha (TNF-alpha), which is released after lipopolysaccharide recognition by TLR4.
To estimate the allele/genotype frequencies and linkage disequilibrium measures of Asp299Gly and Thr399Ile polymorphisms of the TLR4 gene in the Chilean elderly population, and to screen for their association with variables related to adiposity or bone mineral density.
The study group included 227 unrelated Chilean elderly women (61-95 years) recruited from a population-based sample. Adiposity and bone mineral density measures were obtained using dual-energy X-ray absorptiometry.
The allele frequencies for TNF -308A, TLR4 299Gly and TLR4 -399Ile were 9.3%, 4.6% and 4.4%, respectively, with Asp299Gly and Thr399Ile being in strong linkage disequilibrium (D' = 0.88). Although seriously restricted by the low frequency of the allele variants, no relevant association between genotypes and adiposity-related variables were found. Likewise, no significant association between osteoporosis status (categorized as osteoporosis, osteopenia or normal status) with TLR4 Asp299Gly or TNF -308G>A genotypes was found.
It is unlikely that TLR4 Asp299Gly, TLR4 Thr399Ile or TNF -308G>A polymorphisms have a major influence on adiposity, bone mineral density or osteoporosis status in Chilean elderly women.
有人提出,除了在免疫反应中发挥的众所周知的作用外,Toll样受体4基因(TLR4)可能参与肥胖和骨质疏松症的发展。另一方面,肥胖受试者的脂肪组织中促炎细胞因子肿瘤坏死因子-α(TNF-α)的表达增加,该因子在TLR4识别脂多糖后释放。
估计智利老年人群中TLR4基因Asp299Gly和Thr399Ile多态性的等位基因/基因型频率及连锁不平衡指标,并筛查它们与肥胖或骨矿物质密度相关变量的关联。
研究组包括从基于人群的样本中招募的227名无亲缘关系的智利老年女性(61 - 95岁)。使用双能X线吸收法测量肥胖和骨矿物质密度。
TNF - 308A、TLR4 299Gly和TLR4 - 399Ile的等位基因频率分别为9.3%、4.6%和4.4%,Asp299Gly和Thr399Ile处于强连锁不平衡状态(D' = 0.88)。尽管受等位基因变异低频的严重限制,但未发现基因型与肥胖相关变量之间的相关关联。同样,未发现骨质疏松状态(分为骨质疏松、骨量减少或正常状态)与TLR4 Asp299Gly或TNF - 308G>A基因型之间存在显著关联。
TLR4 Asp299Gly、TLR4 Thr399Ile或TNF - 308G>A多态性不太可能对智利老年女性的肥胖、骨矿物质密度或骨质疏松状态产生重大影响。