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Published in: BMC Pulmonary Medicine 1/2009

Open Access 01-12-2009 | Research article

Association of the TLR4 Asp299Gly polymorphism with lung function in relation to body mass index

Authors: Punam Pahwa, Chandima P Karunanayake, Donna C Rennie, Yue Chen, David A Schwartz, James A Dosman

Published in: BMC Pulmonary Medicine | Issue 1/2009

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Abstract

Background

Previous studies have shown conflicting results for the association between TLR4 polymorphism (Asp299Gly) and lung function. We investigated the influence of TLR4 Asp299Gly, a polymorphism, on lung function in a community population.

Methods

In 2003, a cross-sectional survey was conducted to assess the respiratory health of residents living in and around the town of Humboldt, Saskatchewan, Canada. There were 2090 adults age 18-79 years who completed a questionnaire that included a medical and smoking history, as well as socio-economic and lifestyle variables. Genetic information and lung function test measurements were available on 1725 subjects (754 males and 971 females) of the 2090 respondents. These subjects were selected for further analysis to investigate the association between TLR4 Asp299Gly genotype and forced expiratory volume in the first second in liters (FEV1), forced vital capacity in liters (FVC), FEV1/FVC ratio, and forced expiratory flow rate in liters/second (FEF25-75). Multivariable linear regression analysis was used to investigate associations.

Results

Adjusted mean values of FEV1 and FVC were significantly different between TLR4 wild type and TLR4 variant groups [Mean ± S.E.: (TLR4 wild type - FEV1: 3.18 ± 0.02, FVC: 3.95 ± 0.03; TLR4 variant - FEV1: 3.31 ± 0.06, FVC: 4.14 ± 0.07)]. Based on multivariable regression analysis, we observed that body mass index (BMI) was associated with decreased FEV1/FVC ratio and FEF25-75 in TLR4 variant group but not in wild type group.

Conclusion

BMI may modify the associations of TLR4 Asp299Gly polymorphism with FEV1/FVC ratio and FEF25-75.
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Literature
1.
go back to reference Aderem A, Ulevitch RJ: Toll-like receptors in the induction of the innate immune response. Nature. 2000, 406: 782-787. 10.1038/35021228.CrossRefPubMed Aderem A, Ulevitch RJ: Toll-like receptors in the induction of the innate immune response. Nature. 2000, 406: 782-787. 10.1038/35021228.CrossRefPubMed
2.
go back to reference Raby BA, Klimecki WT, Laprise C, Renaud Y, Faith J, Lemire M, Greenwood C, Weiland KM, Lange C, Palmer LJ, Lazarus R, Vercelli D, Kwiatkowski DJ, Silverman EK, Martinez FD, Hudson TJ, Weiss ST: Polymorphisms in toll-like receptor 4 are not associated with asthma or atopy-related phenotypes. Am J Respir Crit Care Med. 2002, 166: 1449-1456. 10.1164/rccm.200207-634OC.CrossRefPubMed Raby BA, Klimecki WT, Laprise C, Renaud Y, Faith J, Lemire M, Greenwood C, Weiland KM, Lange C, Palmer LJ, Lazarus R, Vercelli D, Kwiatkowski DJ, Silverman EK, Martinez FD, Hudson TJ, Weiss ST: Polymorphisms in toll-like receptor 4 are not associated with asthma or atopy-related phenotypes. Am J Respir Crit Care Med. 2002, 166: 1449-1456. 10.1164/rccm.200207-634OC.CrossRefPubMed
3.
go back to reference Michel O, LeVan T, Stern D, Dentener M, Thorn J, Gnat D, Beijer ML, Cochaux P, Holt PG, Martinez FD, Rylander R: Systemic responsiveness to lipopolysaccharide and polymorphisms in the toll-like receptor 4 gene in human beings. J Allergy Clin Immunol. 2003, 112: 923-929. 10.1016/j.jaci.2003.05.001.CrossRefPubMed Michel O, LeVan T, Stern D, Dentener M, Thorn J, Gnat D, Beijer ML, Cochaux P, Holt PG, Martinez FD, Rylander R: Systemic responsiveness to lipopolysaccharide and polymorphisms in the toll-like receptor 4 gene in human beings. J Allergy Clin Immunol. 2003, 112: 923-929. 10.1016/j.jaci.2003.05.001.CrossRefPubMed
4.
go back to reference Sandford AJ, Joos L, Pare PD: Genetic risk factors for chronic obstructive pulmonary disease. Curr Opin Pulm Med. 2002, 8: 87-94. 10.1097/00063198-200203000-00002.CrossRefPubMed Sandford AJ, Joos L, Pare PD: Genetic risk factors for chronic obstructive pulmonary disease. Curr Opin Pulm Med. 2002, 8: 87-94. 10.1097/00063198-200203000-00002.CrossRefPubMed
5.
go back to reference Hang J, Zhou W, Zhang H, Sun B, Dai H, Su L, Christiani DC: TLR4 Asp299Gly andThr399Ile polymorphisms are very rare in the Chinese population. J Endotoxin Res. 2004, 10 (4): 238-240. 10.1179/096805104225005841.CrossRefPubMed Hang J, Zhou W, Zhang H, Sun B, Dai H, Su L, Christiani DC: TLR4 Asp299Gly andThr399Ile polymorphisms are very rare in the Chinese population. J Endotoxin Res. 2004, 10 (4): 238-240. 10.1179/096805104225005841.CrossRefPubMed
6.
go back to reference Basu S, Fenton MJ: Toll-like receptors: functions and roles in lung disease. Am J Physiol Lung Cell Mol Physiol. 2004, 286: L887-L892. 10.1152/ajplung.00323.2003.CrossRefPubMed Basu S, Fenton MJ: Toll-like receptors: functions and roles in lung disease. Am J Physiol Lung Cell Mol Physiol. 2004, 286: L887-L892. 10.1152/ajplung.00323.2003.CrossRefPubMed
7.
go back to reference Arbour NC, Lorenz E, Schutte BC, Zabner J, Kline JN, Jones M, Frees K, Watt JL, Schwartz DA: TLR4 mutation is associated with endotoxin hyporesponsiveness in humans. Nature Genetics. 2000, 25: 187-191. 10.1038/76048.CrossRefPubMed Arbour NC, Lorenz E, Schutte BC, Zabner J, Kline JN, Jones M, Frees K, Watt JL, Schwartz DA: TLR4 mutation is associated with endotoxin hyporesponsiveness in humans. Nature Genetics. 2000, 25: 187-191. 10.1038/76048.CrossRefPubMed
8.
go back to reference Eisenbarth SC, Piggott DA, Huleatt JW, Visintin I, Herrick CA, Bottomly K: Lipopolysaccharide-enhanced, toll-like receptor 4-dependent T helper cell type 2 responses to inhaled antigen. J Exp Med. 2002, 196: 1645-1651. 10.1084/jem.20021340.CrossRefPubMedPubMedCentral Eisenbarth SC, Piggott DA, Huleatt JW, Visintin I, Herrick CA, Bottomly K: Lipopolysaccharide-enhanced, toll-like receptor 4-dependent T helper cell type 2 responses to inhaled antigen. J Exp Med. 2002, 196: 1645-1651. 10.1084/jem.20021340.CrossRefPubMedPubMedCentral
9.
go back to reference LeVan TD, Von Essen S, Romberger DJ, Lambert GP, Martinez FD, Vasquez MM, Merchant JA: Polymorphisms in the CD14 Gene Associated with Pulmonary Function in Farmers. Am J Resp Crit Care Med. 2005, 171: 773-779. 10.1164/rccm.200404-530OC.CrossRefPubMed LeVan TD, Von Essen S, Romberger DJ, Lambert GP, Martinez FD, Vasquez MM, Merchant JA: Polymorphisms in the CD14 Gene Associated with Pulmonary Function in Farmers. Am J Resp Crit Care Med. 2005, 171: 773-779. 10.1164/rccm.200404-530OC.CrossRefPubMed
10.
go back to reference Santos JL, Lera L, Pérez-Bravo F, Albala C: Adiposity and bone mineral density of Chilean elderly women in relation to toll-like receptor 4 gene polymorphisms. Ann Hum Biol. 2006, 33 (5-6): 585-592. 10.1080/03014460601011798.CrossRefPubMed Santos JL, Lera L, Pérez-Bravo F, Albala C: Adiposity and bone mineral density of Chilean elderly women in relation to toll-like receptor 4 gene polymorphisms. Ann Hum Biol. 2006, 33 (5-6): 585-592. 10.1080/03014460601011798.CrossRefPubMed
11.
go back to reference Illig T, Bongardt F, Schöfer A, Holle R, Muller A, Rathmann W, Koenig W, Meisinger C, Wichmann H-E, Kolb H: The endotoxin receptor TLR4 polymorphism is not associated with diabetes or components of the metabolic syndrome. Diabetes. 2003, 52: 2861-2964. 10.2337/diabetes.52.11.2861.CrossRefPubMed Illig T, Bongardt F, Schöfer A, Holle R, Muller A, Rathmann W, Koenig W, Meisinger C, Wichmann H-E, Kolb H: The endotoxin receptor TLR4 polymorphism is not associated with diabetes or components of the metabolic syndrome. Diabetes. 2003, 52: 2861-2964. 10.2337/diabetes.52.11.2861.CrossRefPubMed
12.
go back to reference Medarov BI, Strachan P, Cohen R: Effect of body mass index on pulmonary function tests. Chest. 2005, 128 (4): 171S-172S. Medarov BI, Strachan P, Cohen R: Effect of body mass index on pulmonary function tests. Chest. 2005, 128 (4): 171S-172S.
13.
go back to reference Jones RL, Nzekwu MMU: The Effects of Body Mass Index on Lung Volumes. Chest. 2006, 130: 827-833. 10.1378/chest.130.3.827.CrossRefPubMed Jones RL, Nzekwu MMU: The Effects of Body Mass Index on Lung Volumes. Chest. 2006, 130: 827-833. 10.1378/chest.130.3.827.CrossRefPubMed
14.
go back to reference Chen Y, Rennie D, Cormier YF, Dosman J: Waist circumference is associated with pulmonary function in normal-weight, overweight, and obese subjects. Am J Clin Nutr. 2007, 85: 35-39.PubMed Chen Y, Rennie D, Cormier YF, Dosman J: Waist circumference is associated with pulmonary function in normal-weight, overweight, and obese subjects. Am J Clin Nutr. 2007, 85: 35-39.PubMed
15.
go back to reference Carey IM, Cook DG, Strachan DP: The effects of adiposity and weight change on forced expiratory volume decline in a longitudinal study of adults. Int J Obesity. 1999, 23: 979-985. 10.1038/sj.ijo.0801029.CrossRef Carey IM, Cook DG, Strachan DP: The effects of adiposity and weight change on forced expiratory volume decline in a longitudinal study of adults. Int J Obesity. 1999, 23: 979-985. 10.1038/sj.ijo.0801029.CrossRef
16.
go back to reference Lin WY, Yao CA, Wang HC, Huang KC: Impaired lung function is associated with obesity and metabolic syndrome in adults. Obesity. 2006, 14 (9): 1654-1661. 10.1038/oby.2006.190.CrossRefPubMed Lin WY, Yao CA, Wang HC, Huang KC: Impaired lung function is associated with obesity and metabolic syndrome in adults. Obesity. 2006, 14 (9): 1654-1661. 10.1038/oby.2006.190.CrossRefPubMed
17.
go back to reference Shen W, Punyanitya M, Chen J, Gallagher D, Albu J, Pi-Sunyer X, Lewis CE, Grunfeld C, Heshka Stanley, Heymsfield SB: Waist circumference correlates with metabolic syndrome indicators better than percentage fat. Obesity. 2006, 14 (4): 727-736. 10.1038/oby.2006.83.CrossRefPubMedPubMedCentral Shen W, Punyanitya M, Chen J, Gallagher D, Albu J, Pi-Sunyer X, Lewis CE, Grunfeld C, Heshka Stanley, Heymsfield SB: Waist circumference correlates with metabolic syndrome indicators better than percentage fat. Obesity. 2006, 14 (4): 727-736. 10.1038/oby.2006.83.CrossRefPubMedPubMedCentral
18.
go back to reference Chen Y, Rennie DC, Cormier Y, Dosman J: Sex specificity of asthma associated with objectively measured body mass index and waist circumference: The Humboldt Study. Chest. 2005, 128: 3048-3054. 10.1378/chest.128.4.3048.CrossRefPubMed Chen Y, Rennie DC, Cormier Y, Dosman J: Sex specificity of asthma associated with objectively measured body mass index and waist circumference: The Humboldt Study. Chest. 2005, 128: 3048-3054. 10.1378/chest.128.4.3048.CrossRefPubMed
19.
go back to reference Standardization of Spirometry-1994 update. American Thoracic Society. Am J Respir Crit Care Med. 1995, 152: 1107-1646. Standardization of Spirometry-1994 update. American Thoracic Society. Am J Respir Crit Care Med. 1995, 152: 1107-1646.
20.
go back to reference Crapo RO, Morris AH, Clayton PD, Nixon CR: Lung volumes in healthy nonsmoking Adults. Bull Europ Physiopathol Respir. 1982, 18: 419-425. Crapo RO, Morris AH, Clayton PD, Nixon CR: Lung volumes in healthy nonsmoking Adults. Bull Europ Physiopathol Respir. 1982, 18: 419-425.
21.
go back to reference Schwartz DA: TLR4 and LPS hyporesponsiveness in humans. Int J Hyg Environ Health. 2002, 205: 221-227. 10.1078/1438-4639-00117.CrossRefPubMed Schwartz DA: TLR4 and LPS hyporesponsiveness in humans. Int J Hyg Environ Health. 2002, 205: 221-227. 10.1078/1438-4639-00117.CrossRefPubMed
22.
go back to reference Hosmer DW, Lemshow S: Applied Logistic Regression. 1989, A Wiley-Interscience Publication, John Wiley and Sons Inc., Canada, 82-134. Hosmer DW, Lemshow S: Applied Logistic Regression. 1989, A Wiley-Interscience Publication, John Wiley and Sons Inc., Canada, 82-134.
23.
go back to reference Pistelli F, Bottai M, Carrozzi L, Di Pede F, Baldacci S, Maio S, Brusasco V, Pellegrino R, Viegi G: Changes in obesity status and lung function decline in a general population sample. Respir Med. 2008, 102 (5): 674-680. 10.1016/j.rmed.2007.12.022.CrossRefPubMed Pistelli F, Bottai M, Carrozzi L, Di Pede F, Baldacci S, Maio S, Brusasco V, Pellegrino R, Viegi G: Changes in obesity status and lung function decline in a general population sample. Respir Med. 2008, 102 (5): 674-680. 10.1016/j.rmed.2007.12.022.CrossRefPubMed
24.
go back to reference Ochs-Balcom HM, Grant BJB, Muti P, Sempos CT, Freudenheim JL, Trevisan M, Cassano PA, Iacoviello L, Schünemann HJ: Pulmonary function and abdominal adiposity in the general population. Chest. 2006, 129: 853-862. 10.1378/chest.129.4.853.CrossRefPubMed Ochs-Balcom HM, Grant BJB, Muti P, Sempos CT, Freudenheim JL, Trevisan M, Cassano PA, Iacoviello L, Schünemann HJ: Pulmonary function and abdominal adiposity in the general population. Chest. 2006, 129: 853-862. 10.1378/chest.129.4.853.CrossRefPubMed
25.
go back to reference Rohde G, Klein W, Umut A, Hagedorn M, Duerig N, Bauer T, Gillissen A, Schultze-Werninghaus G, Epplen JT: Association of the ASP299GLY TLR4 polymorphism with COPD. Respir Med. 2006, 100 (5): 892-896. 10.1016/j.rmed.2005.08.018.CrossRefPubMed Rohde G, Klein W, Umut A, Hagedorn M, Duerig N, Bauer T, Gillissen A, Schultze-Werninghaus G, Epplen JT: Association of the ASP299GLY TLR4 polymorphism with COPD. Respir Med. 2006, 100 (5): 892-896. 10.1016/j.rmed.2005.08.018.CrossRefPubMed
26.
go back to reference Yamada Y, Ichihara S, Kato K, Yoshida T, Yokoi K, Matsuo H, Watanabe S, Metoki N, Yoshida H, Satoh K, Aoyagi Y, Yasunaga A, Park H, Tanaka M, Lee W, Nozawa Y: Genetic risk for metabolic syndrome: examination of candidate gene polymorphisms related to lipid metabolism in Japanese people. J Med Genetics. 2008, 45: 22-26. 10.1136/jmg.2007.052415.CrossRef Yamada Y, Ichihara S, Kato K, Yoshida T, Yokoi K, Matsuo H, Watanabe S, Metoki N, Yoshida H, Satoh K, Aoyagi Y, Yasunaga A, Park H, Tanaka M, Lee W, Nozawa Y: Genetic risk for metabolic syndrome: examination of candidate gene polymorphisms related to lipid metabolism in Japanese people. J Med Genetics. 2008, 45: 22-26. 10.1136/jmg.2007.052415.CrossRef
27.
go back to reference Grundy SM, Brewer HB, Cleeman JI, Smith SC, Lenfant C, for the Conference Participants: Definition of Metabolic Syndrome. Circulation. 2004, 109: 433-438. 10.1161/01.CIR.0000111245.75752.C6.CrossRefPubMed Grundy SM, Brewer HB, Cleeman JI, Smith SC, Lenfant C, for the Conference Participants: Definition of Metabolic Syndrome. Circulation. 2004, 109: 433-438. 10.1161/01.CIR.0000111245.75752.C6.CrossRefPubMed
28.
go back to reference Veltkamp M, Grutters JC, van Moorsel CHM, Bosch van den : Toll-like receptor (TLR) 4 polymorphism Asp299Gly is not associated with disease course in Dutch sarcoidosis patients. J Clin Microbiol. 2005, 145: 215-218. Veltkamp M, Grutters JC, van Moorsel CHM, Bosch van den : Toll-like receptor (TLR) 4 polymorphism Asp299Gly is not associated with disease course in Dutch sarcoidosis patients. J Clin Microbiol. 2005, 145: 215-218.
29.
go back to reference Ioannidis JPA, Boffetta P, Little J, O'Brien TR, Uitterlinden AG, Vineis P, Balding DJ, Chokkalingam A, Dolan SM, Flanders WD, Higgins JPT, McCarthy MI, McDermott DH, Page GP, Rebbeck TR, Seminara , Khoury MJ: Assessment of cumulative evidence on genetic associations: interim guidelines. Int J Epidemiol. 2008, 37: 120-132. 10.1093/ije/dym159.CrossRefPubMed Ioannidis JPA, Boffetta P, Little J, O'Brien TR, Uitterlinden AG, Vineis P, Balding DJ, Chokkalingam A, Dolan SM, Flanders WD, Higgins JPT, McCarthy MI, McDermott DH, Page GP, Rebbeck TR, Seminara , Khoury MJ: Assessment of cumulative evidence on genetic associations: interim guidelines. Int J Epidemiol. 2008, 37: 120-132. 10.1093/ije/dym159.CrossRefPubMed
Metadata
Title
Association of the TLR4 Asp299Gly polymorphism with lung function in relation to body mass index
Authors
Punam Pahwa
Chandima P Karunanayake
Donna C Rennie
Yue Chen
David A Schwartz
James A Dosman
Publication date
01-12-2009
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2009
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/1471-2466-9-46

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