Variants in ADIPOQ gene are linked to adiponectin levels and lung function in young males independent of obesity

Autoři: Andria Christodoulou aff001;  Despo Ierodiakonou aff002;  Awoyemi A. Awofala aff003;  Michael Petrou aff004;  Stefanos N. Kales aff005;  David C. Christiani aff005;  Christos S. Mantzoros aff007;  Costas A. Christophi aff001
Působiště autorů: Cyprus International Institute for Environmental and Public Health, Cyprus University of Technology, Limassol, Cyprus aff001;  Department of Social Medicine Faculty of Medicine, University of Crete, Crete, Greece aff002;  Department of Biological Sciences, Tai Solarin University of Education, Ijagun, Ogun State, Nigeria aff003;  Cyprus Anti-doping Authority, Nicosia, Cyprus aff004;  Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, United States of America aff005;  Cambridge Health Alliance, Harvard Medical School, Cambridge, MA, United States of America aff006;  Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States of America aff007
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article



Obesity is a major risk factor for many chronic diseases, including reduced lung function. The role of polymorphisms of the adiponectin gene, though linked with cardiometabolic consequences of obesity, has not been studied in relation to lung function.


The aim of this study is to examine polymorphisms in the ADIPOQ, ADIPOR1, and ADIPOR2 genes in relation to adiponectin serum levels, BMI, and adiposity in 18-year old Cypriot males, as well as determine whether BMI, adipokines levels and polymorphisms in adipokine related genes are associated with lung function levels.


From the participants, 8% were classified as obese, 22% as overweight, and the remaining 71% as normal. We found that rs266729 and rs1501299 in ADIPOQ and rs10920531 in ADIPOR1 were significantly associated with serum adiponectin levels, after adjusting for ever smoking. In addition, there was an overall significant increase in FEV1% predicted with increasing BMI (β = 0.53, 95% CI: 0.27, 0.78) and in FVC % predicted (β = 1.02, 95% CI: 0.73, 1.30). There was also a decrease in FEV1/FVC with increasing BMI (β = -0.53, 95% CI: -0.71, -0.35). Finally, rs1501299 was associated with lung function measures.


Functional variants in the ADIPOQ gene were linked with lung function in young males. Further studies should concentrate on the role of adipokines on lung function which may direct novel therapeutic approaches.

Klíčová slova:

Adipokines – Adiponectin – Body Mass Index – Cyprus – Genome-wide association studies – Obesity – Pulmonary function – Variant genotypes


1. Home. May 2018. Accessed May 8, 2018.

2. Seidell JC, Halberstadt J. The global burden of obesity and the challenges of prevention. Ann Nutr Metab. 2015;66 Suppl 2(Suppl. 2):7–12. doi: 10.1159/000375143 26045323

3. Andreou E, Hajigeorgiou P, Kyriakou K, et al. Risk factors of obesity in a cohort of 1001 Cypriot adults: An epidemiological study. Hippokratia. 2012;16(3):256–260. Accessed November 29, 2016. 23935294

4. Van Gaal LF, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease. Nature. 2006;444(7121):875–880. doi: 10.1038/nature05487 17167476

5. McCarthy MI. Genomics, Type 2 Diabetes, and Obesity. Feero WG, Guttmacher AE, eds. N Engl J Med. 2010;363(24):2339–2350. doi: 10.1056/NEJMra0906948 21142536

6. Adams KF, Schatzkin A, Harris TB, et al. Overweight, Obesity, and Mortality in a Large Prospective Cohort of Persons 50 to 71 Years Old. N Engl J Med. 2006;355(8):763–778. doi: 10.1056/NEJMoa055643 16926275

7. Rizvi AA. Hypertension, Obesity, and Inflammation: The Complex Designs of a Deadly Trio. Metab Syndr Relat Disord. 2010;8(4):287–294. doi: 10.1089/met.2009.0116 20367224

8. Liu P-C, Kieckhefer GM, Gau B-S. A systematic review of the association between obesity and asthma in children. J Adv Nurs. 2013;69(7):1446–1465. doi: 10.1111/jan.12129 23560878

9. Melo LC, Silva MAM da, Calles AC do N. Obesity and lung function: a systematic review. Einstein (Sao Paulo). 12(1):120–125. Accessed January 29, 2018.

10. Winck AD, Heinzmann‐Filho JP, Soares RB, da Silva JS, Woszezenki CT, Zanatta LB. Efeitos da obesidade sobre os volumes e as capacidades pulmonares em crianças e adolescentes: uma revisão sistemática. Rev Paul Pediatr. 2016;34(4):510–517. doi: 10.1016/j.rpped.2016.02.008 27130483

11. Chen Y, Horne SL, Dosman JA. Body weight and weight gain related to pulmonary function decline in adults: A six year follow up study. Thorax. 1993. doi: 10.1136/thx.48.4.375 8511735

12. Jartti T, Saarikoski L, Jartti L, et al. Obesity, adipokines and asthma. Allergy. 2009;64(5):770–777. doi: 10.1111/j.1398-9995.2008.01872.x 19210351

13. Balsan GA, Vieira JL da C, Oliveira AM de, et al. Relationship between adiponectin, obesity and insulin resistance. Rev Assoc Med Bras. 2015;61(1):72–80. doi: 10.1590/1806-9282.61.01.072 25909213

14. Salah A, Ragab M, Mansour W, Taher M. Leptin and adiponectin are valuable serum markers explaining obesity/bronchial asthma interrelationship. Egypt J Chest Dis Tuberc. 2015;64(3):529–533. doi: 10.1016/J.EJCDT.2015.02.012

15. Thyagarajan B, Jacobs DR, Smith LJ, et al. Serum adiponectin is positively associated with lung function in young adults, independent of obesity: the CARDIA study. Respir Res. 2010;11(1):176. doi: 10.1186/1465-9921-11-176 21143922

16. Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003;423(6941):762–769. doi: 10.1038/nature01705 12802337

17. Henneman P, Aulchenko YS, Frants RR, et al. Genetic architecture of plasma adiponectin overlaps with the genetics of metabolic syndrome-related traits. Diabetes Care. 2010;33(4):908–913. doi: 10.2337/dc09-1385 20067957

18. Antoniades C, Antonopoulos AS, Tousoulis D, Stefanadis C. Adiponectin: from obesity to cardiovascular disease. Obes Rev. 2009;10(3):269–279. doi: 10.1111/j.1467-789X.2009.00571.x 19389061

19. Li S, Shin HJ, Ding EL, van Dam RM. Adiponectin Levels and Risk of Type 2 Diabetes. JAMA. 2009;302(2):179. doi: 10.1001/jama.2009.976 19584347

20. Heid IM, Henneman P, Hicks A, et al. Clear detection of ADIPOQ locus as the major gene for plasma adiponectin: Results of genome-wide association analyses including 4659 European individuals. Atherosclerosis. 2010;208(2):412–420. doi: 10.1016/j.atherosclerosis.2009.11.035 20018283

21. Menzaghi C, Trischitta V, Doria A. Genetic Influences of Adiponectin on Insulin Resistance, Type 2 Diabetes, and Cardiovascular Disease. Diabetes. 2007;56(5):1198–1209. doi: 10.2337/db06-0506 17303804

22. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005;21(2):263–265. doi: 10.1093/bioinformatics/bth457 15297300

23. Cupples LA, Arruda HT, Benjamin EJ, et al. The Framingham Heart Study 100K SNP genome-wide association study resource: overview of 17 phenotype working group reports. BMC Med Genet. 2007;8(Suppl 1):S1. doi: 10.1186/1471-2350-8-S1-S1 17903291

24. Hivert M-F, Manning AK, McAteer JB, et al. Common variants in the adiponectin gene (ADIPOQ) associated with plasma adiponectin levels, type 2 diabetes, and diabetes-related quantitative traits: the Framingham Offspring Study. Diabetes. 2008;57(12):3353–3359. doi: 10.2337/db08-0700 18776141

25. Ukkola O, Santaniemi M, Rankinen T, et al. Adiponectin polymorphisms, adiposity and insulin metabolism: HERITAGE family study and Oulu diabetic study. Ann Med. 2005;37(2):141–150. Accessed December 4, 2016. doi: 10.1080/07853890510007241 16028335

26. Loos RJF, Ruchat S, Rankinen T, Tremblay A, Pérusse L, Bouchard C. Adiponectin and adiponectin receptor gene variants in relation to resting metabolic rate, respiratory quotient, and adiposity-related phenotypes in the Quebec Family Study. Am J Clin Nutr. 2007;85(1):26–34. Accessed December 4, 2016. doi: 10.1093/ajcn/85.1.26 17209173

27. Cohen SS, Gammon MD, North KE, et al. ADIPOQ, ADIPOR1, and ADIPOR2 polymorphisms in relation to serum adiponectin levels and BMI in black and white women. Obesity (Silver Spring). 2011;19(10):2053–2062. doi: 10.1038/oby.2010.346 21273992

28. Ling H, Waterworth DM, Stirnadel HA, et al. Genome-wide linkage and association analyses to identify genes influencing adiponectin levels: the GEMS Study. Obesity (Silver Spring). 2009;17(4):737–744. doi: 10.1038/oby.2008.625 19165155

29. Mather KJ, Christophi CA, Jablonski KA, et al. Common variants in genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1/2), adiponectin concentrations, and diabetes incidence in the Diabetes Prevention Program. Diabet Med. 2012;29(12):1579–1588. doi: 10.1111/j.1464-5491.2012.03662.x 22443353

30. Jee SH, Sull JW, Lee J-E, et al. Adiponectin concentrations: a genome-wide association study. Am J Hum Genet. 2010;87(4):545–552. doi: 10.1016/j.ajhg.2010.09.004 20887962

31. Stumvoll M, Tschritter O, Fritsche A, et al. Association of the T-G polymorphism in adiponectin (exon 2) with obesity and insulin sensitivity: interaction with family history of type 2 diabetes. Diabetes. 2002;51(1):37–41. Accessed May 8, 2018. doi: 10.2337/diabetes.51.1.37 11756320

32. Yang W-S, Tsou P-L, Lee W-J, et al. Allele-specific differential expression of a common adiponectin gene polymorphism related to obesity. J Mol Med. 2003;81(7):428–434. doi: 10.1007/s00109-002-0409-4 12750819

33. Sutton BS, Weinert S, Langefeld CD, et al. Genetic analysis of adiponectin and obesity in Hispanic families: the IRAS Family Study. Hum Genet. 2005;117(2–3):107–118. doi: 10.1007/s00439-005-1260-9 15843989

34. Warodomwichit D, Shen J, Arnett DK, et al. ADIPOQ Polymorphisms, Monounsaturated Fatty Acids, and Obesity Risk: The GOLDN Study. Obesity. 2009;17(3):510–517. doi: 10.1038/oby.2008.583 19238139

35. Bekkers MB, Wijga AH, Gehring U, et al. BMI, waist circumference at 8 and 12 years of age and FVC and FEV1 at 12 years of age; the PIAMA birth cohort study. BMC Pulm Med. 2015;15(1):39. doi: 10.1186/s12890-015-0032-0 25896340

36. Cibella F, Bruno A, Cuttitta G, et al. An Elevated Body Mass Index Increases Lung Volume but Reduces Airflow in Italian Schoolchildren. Cormier SA, ed. PLoS One. 2015;10(5):e0127154. doi: 10.1371/journal.pone.0127154 25970463

37. Henrique Tenório LS, da Cruz Santos A, Sarmento de Oliveira A, Myrna de Lima AJ, do Socorro Brasileiro-Santos M. Obesity and pulmonary function tests in children and adolescents: a systematic review. Rev Paul Pediatr. 2012;30(3):423–430. Accessed June 28, 2018.

38. Thyagarajan B, Jacobs DR Jr, Smith LJ, Kalhan R, Gross MD, Sood A. Serum adiponectin is positively associated with lung function in young adults, independent of obesity: The CARDIA study. Respir Res. 2010;11:176. doi: 10.1186/1465-9921-11-176 21143922

39. Guenther M, James R, Marks J, Zhao S, Szabo A, Kidambi S. Adiposity distribution influences circulating adiponectin levels. Transl Res. 2014;164(4):270–277. doi: 10.1016/j.trsl.2014.04.008 24811003

40. Obeidad M, Hao K, Bosse Y, et al. Molecular mechanisms underlying variations in lung function: a systems genetics analysis. Lancet Respir Med. 2015;3:782–795. doi: 10.1016/S2213-2600(15)00380-X 26404118

41. Perneger TV. What’s wrong with Bonferroni adjustments. BMJ. 1998;316:1236–1238. doi: 10.1136/bmj.316.7139.1236 9553006

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