J L Santos1, L Lera, F Pérez-Bravo, C Albala. 1. Laboratory of Genetic and Nutrition Epidemiology, Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago, Chile. jsantos@inta.cl
Abstract
BACKGROUND: 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. AIM: 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. SUBJECTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: 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. AIM: 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. SUBJECTS AND METHODS: 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. RESULTS: 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 TLR4Asp299Gly or TNF -308G>A genotypes was found. CONCLUSION: It is unlikely that TLR4Asp299Gly, TLR4 Thr399Ile or TNF -308G>A polymorphisms have a major influence on adiposity, bone mineral density or osteoporosis status in Chilean elderly women.
Authors: Punam Pahwa; Chandima P Karunanayake; Donna C Rennie; Yue Chen; David A Schwartz; James A Dosman Journal: BMC Pulm Med Date: 2009-09-21 Impact factor: 3.317