Neuropeptide Y Gene Promoter -399T/C Polymorphism Increases Risk of Ischemic Stroke

Yıl 2013, , 147 - 150, 01.02.2013

Xue-feng Fu Xin Zhang Dong-jun Wang Bo Zhao Yu-rong Li

https://doi.org/10.5152/balkanmedj.2013.7964

Öz

Background: Several genetic factors underlying ischemic stroke have been identified. Variants of Neuropeptide Y (NPY), whose product plays diverse roles in modulating physiological functions, have been associated with an increased risk of ischemic stroke in South Korean individuals. Aims: We explored the association between a polymorphism in the NPY gene promoter at position -399 and the risk of ischemic stroke in Han Chinese. Study Design: Case-control study. Methods: The polymorphism -399T/C in the promoter of NPY was analysed in 500 patients with ischemic stroke and 500 healthy individuals by amplification and sequencing of this region. Non-conditional logistic regression was used to analyse association between genotypes and the risk of ischemic stroke. Results: Genotype and allele frequencies differed significantly between the ischemic stroke and control groups (P<0.05). Additionally, compared to stroke patients with the TT genotype, those with the CC genotype had a 1.7-times higher risk of ischemic stroke (OR=1.739, 95%CI=1.201-2.520, P=0.003), especially for those who were over 60 years old or male. Individuals with the TC genotype did not have an increased risk of ischemic stroke (P>0.05). Conclusion: The -399T/C polymorphism of the NPY gene is associated with ischemic stroke in Han Chinese individuals, and the CC genotype may be a risk factor for ischemic stroke. Turkish Başlık: Nöropeptid Y Gen Promotoru -399T/C Polimorfizmi İskemik İnme Riskini Artırmaktadır Anahtar Kelimeler: İskemik inme, Nöropeptid Y, Gen polimorfizmleri Arka Plan: İskemik inmenin altında yatan birçok genetik faktör tanımlanmıştır. Ürünleri fizyolojik fonksiyonları modüle etmede çeşitli roller oynayan Nöropeptid Y (NPY) varyantları Güney Koreli kişilerde iskemik inme riskinde artış ile ilişkilendirilmektedir. Amaç: Han Çinlilerinde NPY gen promotoru -399 pozisyonundaki polimorfizm ile iskemik inme riski arasındaki ilişkiyi araştırdık. Çalışma Tasarımı: Olgu kontrol çalışması. Yöntemler: İskemik inmeli 500 hastada ve 500 sağlıklı kişide NPY promotorundaki -399T/C polimorfizmi bu bölgenin amplifikasyon ve sekanslaması ile analiz edildi. Genotipler ile iskemik inme riski arasındaki ilişkiyi analiz etmek için koşulsuz lojistik regresyon kullanıldı. Bulgular: İskemik inme ve kontrol grupları arasında genotip ve allel frekansları anlamlı şekilde farklıydı (P<0.05). Ek olarak, TT genotipi olan inme hastalarına kıyasla CC genotipi olanlarda iskemik inme riski, özellikle 60 yaş üstü olanlarda veya erkeklerde 1.7 kat daha yüksekti (OR=1.739, %95CI=1.201-2.520, P=0.003). TC genotipi olan kişilerde iskemik inme riskinde artış yoktu (P>0.05). Sonuçlar: Han Çinlilerinde NPY geninin -399T/C polimorfizmi iskemik inme ile ilişkilidir ve CC genotipi iskemik inme için bir risk faktörü olabilir.

Anahtar Kelimeler

Ischemic stroke, Neuropeptide Y, Gene polymorphisms

Neuropeptide Y Gene Promoter -399T/C Polymorphism Increases Risk of Ischemic Stroke

Öz

Kaynakça

• TC 231 (2) 213 (6) 016 (0.774-1.334) 0.907 CC 205 (0) 186 (2) 739 (1.201-2.520) 0.003 TT 27 (1) 44 (9) Reference TC 85 (5) 76 (8) 0.872 (0.563-1.351) 0.540 CC 79 (4) 81 (3) 589 (0.898-2.812) 0.112 ≥60 years old TT 37 (0) 57 (1) Reference TC 146 (2) 137 (8) 126 (0.795-1.595) 0.504 CC 126 (8) 105 (1) 0.964 (1.135-3.012) 0.014 Male TT 43 (5) 88 (8) Reference TC 159 (1) 104 (8) 0.748 (0.530-1.056) 0.099 CC 143 (4) 125 (4) 341 (1.513-3.623) 0.001 Female TT 21 (5) 13 (1) Reference TC 72 (5) 109 (56) 0.629 (0.236-1.368) 0.242 CC 62 (0) 61 (3) 0.969 (0.969-2.443) 0.068 149 Balkan Med J 2013; 30: 147-50 Fu et al.
• NPY Polymorphism and Ischemic stroke Feigin VL. Stroke epidemiology in the developing world. Lancet 2001;365:2160-1. [CrossRef]
• Eltzschig HK, Eckle T. Ischemia and reperfusion--from mechanism to translation. Nat Med 2011;17:1391-401. [CrossRef]
• Rodriguez-Hernández A, Josephson AS, Langer D, Lawton MT. Bypass for the prevention of ischemic stroke. World Neurosurg 2011;76:S72-9. [CrossRef]
• Flossmann E, Sehulz UG, Rothwell PM. Systematic review of methods and results of studies of the genetic epidemiology of ischemic stroke. Stroke 2004;35:212-27. [CrossRef]
• Jerrard-Dunne P, Cloud G, Hassan A, Markus HS. Evaluating the genetic component of ischemic stroke subtypes: a family history study. Stroke 2003;34:1364-9. [CrossRef]
• Meschia JF, Worrall BB, Rich SS. Genetic susceptibility to ischemic stroke. Nat Rev Neurol 2011;7:369-78. [CrossRef]
• Lundberg JM, Terenius L, Hökfelt 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;116:477-80. [CrossRef]
• Walker P, Grouzmann E, Burnier M, Waeber B. The role of neuropeptide Y in cardiovaseular regulation. Trends Pharmacol Sci 1991;12:111-5. [CrossRef]
• Erlinge D, Brunkwall J, Edvinsson L. Neuropeptide Y stimulates proliferation of human vascular smooth muscle cells: cooperation with noradrenaline and ATP. Regul Pept 1994;50:259-65. [CrossRef]
• Zukowska-Grojec Z, Karwatowska-Prokopczuk E, Rose W, Rone J, Movafagh S, Ji H, et al. Neuropeptide Y: a novel angiogenic factor from the sympathetic nerves and endothelium. Circ Res 1998;83:187-95. [CrossRef]
• Renner W, Grammer T, Hoffmann MM, Nauck MS, Winkelmann BR, Boehm BO, et al. Association analysis of the polymorphism T1128C in the signal peptide of neuropeptide Y in a Swedish hypertensive population. J Hypertens 2004;22:2398-9. [CrossRef]
• Itokawa M, Arai M, Kato S, Ogata Y, Furukawa A, Haga S, et al. Association between a novel polymorphism in the promoter region of the neuropeptide Y gene and schizophrenia in humans. Neurosei Lett 2003;347:202-4. [CrossRef]
• Shah SH, Freedman NJ, Zhang L, Crosslin DR, Stone DH, Haynes C, et al. Neuropeptide Y Gene polymorphisms Confer Risk of Early-Onset Atherosclerosis. PLoS Genet 2009;5:e1000318. [CrossRef]
• Kharlamov EA, Kharlamov A, Kelly KM. Changes in neuropeptide Y protein expression following photothrombotic brain infarction and epileptogenesis. Brain Res 2007;1127:151-62. [CrossRef]
• Lee C, Kong M. An interactive association of common sequence variants in the neuropeptide Y gene with susceptibility to ischemic stroke. Stroke 2007;38:2663-9. [CrossRef]
• Buckland PR, Hoogendoorn B, Guy CA, Coleman SL, Smith SK, Buxbaum JD, et al. A high proportion of polymorphisms in the promoters of brain expressed genes influences transcriptional activity. Biochim Biophys Acta 2004;1690:238-49.
• Kim NS, Oh SM, Ko MM, Cha MH, Kang BR, Bang OS. Association of the C-399T promoter polymorphism of neuropeptide Y with susceptibility to ischemic stroke. Clin Biochem 2009;42:169970 [CrossRef]
• Yu JT, Yu NN, Gao SS, Song JH, Ma T, Wang ND, et al. Neuropeptide Y polymorphisms and ischemic stroke in Chinese population. Clin Chim Acta 2010;411:242-5. [CrossRef]
• Montaner J, Mendioroz M, Delgado P, García-Berrocoso T, Giralt D, Merino C, et al. Differentiating ischemic from hemorrhagic stroke using plasma biomarkers: the S100B/RAGE pathway. J Proteomics 2012;75:4758-65. [CrossRef]
• Chen SH, Cheung RT. Peripheral and central administration of neuropeptide Y in a rat middle cerebral artery occlusion stroke model reduces cerebral blood flow and increases infarct volume. Brain Res 2002;927:138-43. [CrossRef]
• Mustacchi P. Risk factors in stroke. West J Med 1985;143:186-92.