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Neuropeptide Y gene functional polymorphism influences susceptibility to hypertension in Indian population

Journal of Human Hypertension volume 24, pages 617–622 (2010)Cite this article

Abstract

Hypertension is an independent determinant of cardiovascular risk, a phenotype that usually has a strong genetic component. Neuropeptide Y (NPY) plays an important role in BP homeostasis. The aim of this study was to investigate the possible influence of NPY polymorphisms on hypertension in a South Indian population. A total of 252 subjects (132 controls and 120 hypertensives) were analysed for T1128C, G1258A and A7735G polymorphisms in the NPY gene. Body mass index (BMI), pulse, SBP and DBP were assessed. Direct sequencing of PCR products was adopted for genotyping. All three polymorphisms were found to be in Hardy–Weinberg equilibrium. Additive, dominant and recessive models were tested using multivariate regression analysis. The results of our study reveal a significant association between T1128C and hypertension even after adjusting for age, sex and BMI. The adjusted OR (95% confidence interval) for the recessive model was 0.56 (0.33–0.95). The other two polymorphic sites (G1258A and A7735G) are not associated with hypertension. The Pro7 allele of the T1128C polymorphic site-containing haplotype (CGA) is associated with hypertension (P=0.049), but the combined haplotypes did not show any evidence of haplotype–phenotype association (global P=0.129). These data support the hypothesis that hypertension is influenced by the NPY T1128C polymorphism.

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References

  1. Reddy KS . Hypertension control in developing countries: generic issues. J Hum Hypertens 1996; 10 (Suppl 1): S33–S38.

    PubMed  Google Scholar 

  2. Hypertension study group. Prevalence, awareness, treatment and control of hypertension among the elderly in Bangladesh and India: a multicentre study. Bull World Health Organ 2001; 79 (6): 490–500.

    PubMed Central  Google Scholar 

  3. Smith C . Blood pressures of Sherpa men in modernizing Nepal. Am J Hum Biol 1999; 11 (4): 469–479.

    Article  PubMed  Google Scholar 

  4. Bevan JA, Brayden JE . Nonadrenergic neural vasodilator mechanisms. Circ Res 1987; 60 (3): 309–326.

    Article  CAS  PubMed  Google Scholar 

  5. Tatemoto K, Carlquist M, Mutt V . Neuropeptide Y—a novel brain peptide with structural similarities to peptide YY and pancreatic polypeptide. Nature 1982; 296 (5858): 659–660.

    Article  CAS  PubMed  Google Scholar 

  6. Gray TS, Morley JE . Neuropeptide Y: anatomical distribution and possible function in mammalian nervous system. Life Sci 1986; 38 (5): 389–401.

    Article  CAS  PubMed  Google Scholar 

  7. O′Shea D, Morgan DG, Meeran K, Edwards CM, Turton MD, Choi SJ et al. Neuropeptide Y induced feeding in the rat is mediated by a novel receptor. Endocrinology 1997; 138 (1): 196–202.

    Article  PubMed  Google Scholar 

  8. Lundberg JM, Terenius L, Hokfelt T, Martling CR, Tatemoto K, Mutt V et al. Neuropeptide Y (NPY)-like immunoreactivity in peripheral noradrenergic neurons and effects of NPY on sympathetic function. Acta Physiol Scand 1982; 116 (4): 477–480.

    Article  CAS  PubMed  Google Scholar 

  9. Malmstrom RE . Neuropeptide Y Y1 receptor mechanisms in sympathetic vascular control. Acta Physiol Scand Suppl 1997; 636: 1–55.

    CAS  PubMed  Google Scholar 

  10. Corr L, Burnstock G, Poole-Wilson P . Effects of age and hyperlipidemia on rabbit coronary responses to neuropeptide Y and the interaction with norepinephrine. Peptides 1993; 14 (2): 359–364.

    Article  CAS  PubMed  Google Scholar 

  11. Ullman B, Franco-Cereceda A, Hulting J, Lundberg JM, Sollevi A . Elevation of plasma neuropeptide Y-like immunoreactivity and noradrenaline during myocardial ischaemia in man. J Intern Med 1990; 228 (6): 583–589.

    Article  CAS  PubMed  Google Scholar 

  12. Minth CD, Andrews PC, Dixon JE . Characterization, sequence, and expression of the cloned human neuropeptide Y gene. J Biol Chem 1986; 261 (26): 11974–11979.

    CAS  PubMed  Google Scholar 

  13. Baker E, Hort YJ, Ball H, Sutherland GR, Shine J, Herzog H . Assignment of the human neuropeptide Y gene to chromosome 7p15.1 by nonisotopic in situ hybridization. Genomics 1995; 26 (1): 163–164.

    Article  CAS  PubMed  Google Scholar 

  14. Minth CD, Bloom SR, Polak JM, Dixon JE . Cloning, characterization, and DNA sequence of a human cDNA encoding neuropeptide tyrosine. Proc Natl Acad Sci USA 1984; 81 (14): 4577–4581.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Karvonen MK, Valkonen VP, Lakka TA, Salonen R, Koulu M, Pesonen U et al. Leucine7 to proline7 polymorphism in the preproneuropeptide Y is associated with the progression of carotid atherosclerosis, blood pressure and serum lipids in Finnish men. Atherosclerosis 2001; 159 (1): 145–151.

    Article  CAS  PubMed  Google Scholar 

  16. Niskanen L, Karvonen MK, Valve R, Koulu M, Pesonen U, Mercuri M et al. Leucine 7 to proline 7 polymorphism in the neuropeptide Y gene is associated with enhanced carotid atherosclerosis in elderly patients with type 2 diabetes and control subjects. J Clin Endocrinol Metab 2000; 85 (6): 2266–2269.

    CAS  PubMed  Google Scholar 

  17. Karvonen MK, Pesonen U, Koulu M, Niskanen L, Laakso M, Rissanen A et al. Association of a leucine(7)-to-proline(7) polymorphism in the signal peptide of neuropeptide Y with high serum cholesterol and LDL cholesterol levels. Nat Med 1998; 4 (12): 1434–1437.

    Article  CAS  PubMed  Google Scholar 

  18. Pickering TG . Blood pressure monitoring outside the office for the evaluation of patients with resistant hypertension. Hypertension 1988; 11 (3 Pt 2): II96–I100.

    CAS  PubMed  Google Scholar 

  19. World Health Organization—International Society of Hypertension Guidelines for the Management of Hypertension. Guidelines Sub-Committee. Blood Press Suppl 1999; 1: 9–43.

    Google Scholar 

  20. Thangaraj K, Joshi MB, Reddy AG, Gupta NJ, Chakravarty B, Singh L . CAG repeat expansion in the androgen receptor gene is not associated with male infertility in Indian populations. J Androl 2002; 23 (6): 815–818.

    CAS  PubMed  Google Scholar 

  21. Cubells JF, Kobayashi K, Nagatsu T, Kidd KK, Kidd JR, Calafell F et al. Population genetics of a functional variant of the dopamine beta-hydroxylase gene (DBH). Am J Med Genet 1997; 74 (4): 374–379.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  23. Tzeng JY, Wang CH, Kao JT, Hsiao CK . Regression-based association analysis with clustered haplotypes through use of genotypes. Am J Hum Genet 2006; 78 (2): 231–242.

    Article  CAS  PubMed  Google Scholar 

  24. Niskanen L, Voutilainen-Kaunisto R, Terasvirta M, Karvonen MK, Valve R, Pesonen U et al. Leucine 7 to proline 7 polymorphism in the neuropeptide Y gene is associated with retinopathy in type 2 diabetes. Exp Clin Endocrinol Diabetes 2000; 108 (3): 235–236.

    Article  CAS  PubMed  Google Scholar 

  25. Erkkila AT, Lindi V, Lehto S, Laakso M, Uusitupa MI . Association of leucine 7 to proline 7 polymorphism in the preproneuropeptide Y with serum lipids in patients with coronary heart disease. Mol Genet Metab 2002; 75 (3): 260–264.

    Article  PubMed  Google Scholar 

  26. Wallerstedt SM, Skrtic S, Eriksson AL, Ohlsson C, Hedner T . Association analysis of the polymorphism T1128C in the signal peptide of neuropeptide Y in a Swedish hypertensive population. J Hypertens 2004; 22 (7): 1277–1281.

    Article  CAS  PubMed  Google Scholar 

  27. Yamada Y, Izawa H, Ichihara S, Takatsu F, Ishihara H, Hirayama H et al. Prediction of the risk of myocardial infarction from polymorphisms in candidate genes. N Engl J Med 2002; 347 (24): 1916–1923.

    Article  CAS  PubMed  Google Scholar 

  28. Drube J, Kawamura N, Nakamura A, Ando T, Komaki G, Inada T . No leucine(7)-to-proline(7) polymorphism in the signal peptide of neuropeptide Y in Japanese population or Japanese with alcoholism. Psychiatr Genet 2001; 11 (1): 53–55.

    Article  CAS  PubMed  Google Scholar 

  29. Makino K, Kataoka Y, Hirakawa Y, Ikeda A, Yamauchi A, Oishi AR . A leucine(7)-to-proline(7) polymorphism in the signal peptide of neuropeptide Y was not identified in the Japanese population. J Clin Pharm Ther 2001; 26 (3): 201–203.

    Article  CAS  PubMed  Google Scholar 

  30. Ding B, Bertilsson L, Wahlestedt C . The single nucleotide polymorphism T1128C in the signal peptide of neuropeptide Y (NPY) was not identified in a Korean population. J Clin Pharm Ther 2002; 27 (3): 211–212.

    Article  CAS  PubMed  Google Scholar 

  31. Jia C, Liu Z, Liu T, Ning Y . The T1128C polymorphism of neuropeptide Y gene in a Chinese population. Arch Med Res 2005; 36 (2): 175–177.

    Article  CAS  PubMed  Google Scholar 

  32. Duan S, Gao R, Xing Q, Du J, Liu Z, Chen Q et al. A family-based association study of schizophrenia with polymorphisms at three candidate genes. Neurosci Lett 2005; 379 (1): 32–36.

    Article  CAS  PubMed  Google Scholar 

  33. Bhaskar LV, Thangaraj K, Shah AM, Pardhasaradhi G, Praveen Kumar K, Reddy AG et al. Allelic variation in the NPY gene in 14 Indian populations. J Hum Genet 2007; 52 (7): 592–598.

    Article  CAS  PubMed  Google Scholar 

  34. Pesonen U . NPY L7P polymorphism and metabolic diseases. Regul Pept 2008; 149 (1–3): 51–55.

    Article  CAS  PubMed  Google Scholar 

  35. Mitchell GC, Wang Q, Ramamoorthy P, Whim MD . A common single nucleotide polymorphism alters the synthesis and secretion of neuropeptide Y. J Neurosci 2008; 28 (53): 14428–14434.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Komaru T, Ashikawa K, Kanatsuka H, Sekiguchi N, Suzuki T, Takishima T . Neuropeptide Y modulates vasoconstriction in coronary microvessels in the beating canine heart. Circ Res 1990; 67 (5): 1142–1151.

    Article  CAS  PubMed  Google Scholar 

  37. Solt VB, Brown MR, Kennedy B, Kolterman OG, Ziegler MG . Elevated insulin, norepinephrine, and neuropeptide Y in hypertension. Am J Hypertens 1990; 3 (11): 823–828.

    Article  CAS  PubMed  Google Scholar 

  38. Michalkiewicz M, Michalkiewicz T, Kreulen DL, McDougall SJ . Increased blood pressure responses in neuropeptide Y transgenic rats. Am J Physiol Regul Integr Comp Physiol 2001; 281 (2): R417–R426.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by a grant from Department of Biotechnology, Government of India (grant no. BT/PR3607/SPD/09/261/2003).

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Authors and Affiliations

  1. Centre for Cellular and Molecular Biology, Hyderabad, India

    L V K S Bhaskar, K Thangaraj, K Praveen Kumar, G Pardhasaradhi & L Singh

  2. Department of Anthropology, University of Florida, Gainesville, FL, USA

    A L Non

  3. Anthropological Survey of India, Kolkata, India

    V R Rao

  4. Department of Biomedical Sciences, Sri Ramachandra University, Chennai, India

    L V K S Bhaskar

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  1. L V K S Bhaskar
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Correspondence to V R Rao.

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Bhaskar, L., Thangaraj, K., Non, A. et al. Neuropeptide Y gene functional polymorphism influences susceptibility to hypertension in Indian population. J Hum Hypertens 24, 617–622 (2010). https://doi.org/10.1038/jhh.2009.104

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