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Analysis between nitric oxide synthase 1 (NOS1) and risk of obesity

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Abstract

Nitric oxide (NO), which is produced by NO synthase (NOS), plays to modulate immune function, blood vessel dilatation, neurotransmission, and mechanism of toxicity. Here, we examined whether single nucleotide polymorphisms (SNPs) of the NOS1 gene contribute to the susceptibility for overweight/obesity in Korean population. We recruited 370 subjects (159 control and 211 overweight/obese subjects), genotyped 3 SNPs in NOS1 gene using Affymetrix targeted genotyping chip array, and analyzed genetic data by Haploview4.2 and SPSS 23.0. Among 3 SNPs, 2 SNPs (rs2293048 and rs9658490) showed significant association with overweight/obesity (rs2293048, Fisher’s exact p=0.048 in codominant 2 model, Fisher’s exact p=0.045 in recessive model; rs9658490, p= 0.025, OR=1.830, 95% CI=1.078-3.105 in codominant 1, p=0.037, OR=1.734, 95% CI=1.033-2.910 in dominant model, respectively). In addition, haplotype TCG and TGG was also associated with a susceptibility of obesity (TCG, p=0.019; TGG, p=0.028). In conclusion, our study suggests that NOS1 gene may be related to overweight/obesity in Korean population.

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References

  1. Bouret, S., Levin, B. E. & Ozanne, S. E. Gene-environment interactions controlling energy and glucose homeostasis and the developmental origins of obesity. Physiol Rev 95:47–82 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  2. Flegal, K. M., Carroll, M. D., Ogden, C. L. & Johnson, C. L. Prevalence and trends in obesity among US adults, 1999-2000. JAMA 288:1723–1727 (2002).

    Article  PubMed  Google Scholar 

  3. Yazdi, F. T., Clee, S. M. & Meyre, D. Obesity genetics in mouse and human: back and forth, and back again. PeerJ 3:e856 (2015).

    Article  Google Scholar 

  4. Ma, S. H. et al. Interaction of body mass index and diabetes as modifiers of cardiovascular mortality in a cohort study. J Prev Med Public Health=Yebang Uihakhoe Chi 45:394–401 (2012).

    Article  Google Scholar 

  5. Baillie-Hamilton, P. F. Chemical toxins: a hypothesis to explain the global obesity epidemic. J Altern Complement Med 8:185–192 (2002).

    Article  PubMed  Google Scholar 

  6. Blakemore, A. I. & Froguel, P. Is obesity our genetic legacy? J Clin Endocrinol Metab 93:S51–56 (2008).

    Article  Google Scholar 

  7. Martinez, J. A. Obesity in young Europeans: genetic and environmental influences. Eur J Clin Nutr 54 Suppl 1:S56–60 (2000).

    Article  Google Scholar 

  8. Forstermann, U. & Sessa, W. C. Nitric oxide synthases: regulation and function. Eur Heart J 33:829–837, 837a-837d (2012).

    Article  PubMed  Google Scholar 

  9. Moran, J. M., Ortiz-Ortiz, M. A., Ruiz-Mesa, L. M. & Fuentes, J. M. Nitric oxide in paraquat-mediated toxicity: A review. J Biochem Mol Toxicol 24:402–409 (2010).

    Article  CAS  PubMed  Google Scholar 

  10. Isse, T. et al. Effects of leptin on fasting-induced inhibition of neuronal nitric oxide synthase mRNA in the paraventricular and supraoptic nuclei of rats. Brain Res 846:229–235 (1999).

    Article  CAS  PubMed  Google Scholar 

  11. Ribiere, C. et al. White adipose tissue nitric oxide synthase: a potential source for NO production. Biochem Biophys Res Commun 222:706–712 (1996).

    Article  CAS  PubMed  Google Scholar 

  12. Wu, G. & Meininger, C. J. Regulation of nitric oxide synthesis by dietary factors. Annu Rev Nutr 22:61–86 (2002).

    Article  CAS  PubMed  Google Scholar 

  13. Donato, J., Frazao, R., Fukuda, M., Vianna, C. R. & Elias, C. F. Leptin induces phosphorylation of neuronal nitric oxide synthase in defined hypothalamic neurons. Endocrinology 151:5415–5427 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ueta, Y., Levy, A., Chowdrey, H. S. & Lightman, S. L. Inhibition of hypothalamic nitric oxide synthase gene expression in the rat paraventricular nucleus by food deprivation is independent of serotonin depletion. J Neuroendocrinol 7:861–865 (1995).

    Article  CAS  PubMed  Google Scholar 

  15. Tsutsui, M. et al. Significance of nitric oxide synthases: Lessons from triple nitric oxide synthases null mice. J Pharmacol Sci 127:42–52 (2015).

    Article  CAS  PubMed  Google Scholar 

  16. Saraiva, R. M. et al. Reduced neuronal nitric oxide synthase expression contributes to cardiac oxidative stress and nitroso-redox imbalance in ob/ob mice. Nitric Oxide-Biol Chem 16:331–338 (2007).

    Article  CAS  Google Scholar 

  17. Ou, Y. et al. Effects of octreotide on nitric oxide synthase expression in the small intestine of high fat diet-induced obese rats. Obes Res Clin Pract 6:e263–346 (2012).

    Article  Google Scholar 

  18. Otunctemur, A. et al. The comparison of GLUT-4 and nNOS expression in diabetic and non-diabetic patients with BPH/LUTS. Int Urol Nephrol 47:899–904 (2015).

    Article  CAS  PubMed  Google Scholar 

  19. de Jong, K. et al. NOS1: a susceptibility gene for reduced level of FEV1 in the setting of pesticide exposure. Am J Respir Crit Care Med 190:1188–1190 (2014).

    Article  PubMed  Google Scholar 

  20. Wu, G., Haynes, T. E., Li, H., Yan, W. & Meininger, C. J. Glutamine metabolism to glucosamine is necessary for glutamine inhibition of endothelial nitric oxide synthesis. Biochem J 353:245–252 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wu, G. & Morris, S. M. Arginine metabolism: nitric oxide and beyond. Biochem J 336(Pt 1):1–17 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Baig, M. S. et al. NOS1-derived nitric oxide promotes NF-kappaB transcriptional activity through inhibition of suppressor of cytokine signaling-1. J Exp Med 212:1725–1738 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Fritzsche, K. et al. Metabolic profile and nitric oxide synthase expression of skeletal muscle fibers are altered in patients with type 1 diabetes. Exp Clin Endocrinol Diabetes 116:606–613 (2008).

    Article  CAS  PubMed  Google Scholar 

  24. Umman, B. et al. Identification of gene variants related to the nitric oxide pathway in patients with acute coronary syndrome. Gene 574:76–81 (2015).

    Article  CAS  PubMed  Google Scholar 

  25. Nakata, S. et al. Spontaneous myocardial infarction in mice lacking all nitric oxide synthase isoforms. Circulation 117:2211–2223 (2008).

    Article  CAS  PubMed  Google Scholar 

  26. Wrzosek, M. et al. Impact of obesity and nitric oxide synthase gene G894T polymorphism on essential hypertension. J Physiol Pharmacol 66:681–689 (2015).

    CAS  PubMed  Google Scholar 

  27. Ali, M. I., Chen, X. & Didion, S. P. Heterozygous eNOS deficiency is associated with oxidative stress and endothelial dysfunction in diet-induced obesity. Physiol Rep 3:(2015).

  28. Elizalde, M. et al. Expression of nitric oxide synthases in subcutaneous adipose tissue of nonobese and obese humans. J Lipid Res 41:1244–1251 (2000).

    CAS  PubMed  Google Scholar 

  29. Lifshitz, F. & Lifshitz, J. Z. Globesity: the root causes of the obesity epidemic in the USA and now worldwide. Pediatr Endocrinol Rev 12:17–34 (2014).

    PubMed  Google Scholar 

  30. Kim, H. J. et al. Combined linkage and association analyses identify a novel locus for obesity near PROX1 in Asians. Obesity 21:2405–2412 (2013).

    Article  CAS  PubMed  Google Scholar 

  31. Shabana, N. A. & Hasnain, S. Association of the leptin receptor Gln223 Arg polymorphism with lipid profile in obese Pakistani subjects. Nutrition 31:1136–1140 (2015).

    Article  CAS  PubMed  Google Scholar 

  32. Zhang, M. et al. Age-and sex-dependent association between FTO rs9939609 and obesity-related traits in Chinese children and adolescents. PloS One 9:e97545 (2014).

    Article  Google Scholar 

  33. Rouskas, K. et al. Common variants in FTO, MC4R, TMEM18, PRL, AIF1, and PCSK1 show evidence of association with adult obesity in the Greek population. Obesity 20:389–395 (2012).

    Article  CAS  PubMed  Google Scholar 

  34. Stijnen, P. et al. The association of common variants in PCSK1 with obesity: a HuGE review and meta-analysis. Am J Epidemiol 180:1051–1065 (2014).

    Article  PubMed  Google Scholar 

  35. Liu, C., Mou, S. & Cai, Y. FTO gene variant and risk of overweight and obesity among children and adolescents: a systematic review and meta-analysis. PloS One 8:e82133 (2013).

    Article  Google Scholar 

  36. Thomas, G. D. et al. Impaired metabolic modulation of alpha-adrenergic vasoconstriction in dystrophin-deficient skeletal muscle. Proc Nat’l Acad Sci USA 95:15090–15095 (1998).

    Article  CAS  Google Scholar 

  37. Ban, J. Y. et al. The association of PBX1 polymorphisms with overweight/obesity and metabolic alterations in the Korean population. Nutr Res Pract 2:289–294 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Yoo, S. D. et al. Polymorphism of Nitric Oxide Synthase 1 Affects the Clinical Phenotypes of Ischemic Stroke in Korean Population. Ann Rehabil Med 40:102–110 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Lewis, C. M. Genetic association studies: design, analysis and interpretation. Brief Bioinform 3:146–153 (2002).

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Seong-Kyu Lee.

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Park, H.K., Kim, S.K., Kwon, O.Y. et al. Analysis between nitric oxide synthase 1 (NOS1) and risk of obesity. Mol. Cell. Toxicol. 12, 217–222 (2016). https://doi.org/10.1007/s13273-016-0026-x

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  • DOI: https://doi.org/10.1007/s13273-016-0026-x

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