Association between genetic variation of mitogen-activated protein kinase activated protein kinase 2 gene and metabolic syndrome in Uygur population

( views:166, downloads:0 )
Author:
YAO Xiao-guang(Hypertension center of People's Hospital of Xinjiang Uygur Autonomous Region, Hypertension institute of Xinjiang, Urumqi 830001, China)
LIANG Deng-pan(Hypertension center of People's Hospital of Xinjiang Uygur Autonomous Region, Hypertension institute of Xinjiang, Urumqi 830001, China)
GUO Yan-ying(Hypertension center of People's Hospital of Xinjiang Uygur Autonomous Region, Hypertension institute of Xinjiang, Urumqi 830001, China)
YAN Zhi-tao(Hypertension center of People's Hospital of Xinjiang Uygur Autonomous Region, Hypertension institute of Xinjiang, Urumqi 830001, China)
WANG Hong-mei(Hypertension center of People's Hospital of Xinjiang Uygur Autonomous Region, Hypertension institute of Xinjiang, Urumqi 830001, China)
ZHOU Ling(Hypertension center of People's Hospital of Xinjiang Uygur Autonomous Region, Hypertension institute of Xinjiang, Urumqi 830001, China)
Nuergu li(Hypertension center of People's Hospital of Xinjiang Uygur Autonomous Region, Hypertension institute of Xinjiang, Urumqi 830001, China)
LI Nan-fang(Hypertension center of People's Hospital of Xinjiang Uygur Autonomous Region, Hypertension institute of Xinjiang, Urumqi 830001, China)
Journal Title:
Chinese Journal of Biomedical Engineering
Issue:
Volume 17, Issue 05, 2011
DOI:
10.3760/cma.j.issn.1674-1927.2011.05.002
Key Word:
Mitogen-activated protein kinase;Metabolic syndrome;Uygur;Poly morphism;single nucleotide

Abstract: Objective To examine the association between mitogen- activated protein kinaseactivated protein kinases 2 (MK2) gene variation and metabolic syndrome (MS),so as to provide evidence for molecular genetics study on MS.Methods In this epidemiologic survey-based case-control study,2334Uygur subjects from natural population were enrolled (808 people with MS and 1526 without MS).Genetic variations were sequenced and screened at loci over functional region of MK2 gene in MS subjects.The typical loci were selected for genotyping by TaqMan-PCR method in 2334 Uygur subjects for case-control study.Results Three typicalloci out of the 7 variation loci (4 already known and 3 newly founded)identified at the functional region of MK2 gene were selected for genotyping.There was no statistical difference in genotypic frequency of 2 TaqMan-PCR-identified variation loci (rs45514798,44890c/t)between MS group and non-MS group (P>0.05).However,subjects with GG genotype at rs45514798 had significantly smaller waist circumference [ (85.1 + 11.5)cm ] than those with genotypes AG or AA [ (87.1 +21.7)cm] (t=2.145,P=0.032).According to haplotype association analysis,the frequency of H3 C-A in MS group (12.9%) was higher than that in non-MS group (10.3%) (X2=4.326,P=0.035),and higher in MS females (13.9%) than in non-MS females (10.8%) (x2=3.79,P=0.050).Conclusion Among Urgur population,the polymorphisms of the MK2 gene 44890c/t and rs45514798 are not associated with MS,while the association between waist circumference and rs45514798 polymorphism remains to be further confirmed.

  • [1]Hegen M,Gaestel M,Nickerson-Nutter CL,et al.MAPKAP kinase 2-deficient mice are resistant to collagen-induced arthritis.J Immunol,2006,177:1913-1917.
  • [2]Funding AT,Johansen C,Gaestel M,et al.Reduced oxazoloneinduced skin inflammation in MAPKAP kinase 2 knockout mice.J Invest Dermatol,2009,129:891-898.
  • [3]Jagavelu K,Tietge UJ,Gaestel M,et al.Systemic deficiency of the MAP kinase-activated protein kinase 2 reduces atherosclerosis in hypercholesterolemic mice.Circ Res,2007,101:1104-1112.
  • [4]Culbert AA,Skaper SD,Howlett DR,et al.MAPK-activated protein kinase 2 deficiency in microglia inhibits pro-inflammatory mediator release and resultant neurotoxicity.Relevance to neuroinflammation in a transgenic mouse model of Alzheimer disease.J Biol Chem,2006,281:23658-23667.
  • [5]Kotlyarov A,Neininger A,Schubert C,et al.MAPKAP kinase 2is essential for LPS-induced TNF-alpha biosynthesis.Nat Cell Biol,1999,1:94-97.
  • [6]Hitti E,Iakovleva T,Brook M,et al.Mitogen-activated protein kinase-activated protein kinase 2 regulates tumor necrosis factor mRNA stability and translation mainly by altering tristetraprolin expression,stability,and binding to adenine/uridine-rich element.Mol Cell Biol,2006,26:2399-2407.
  • [7]Neininger A,Kontoyiannis D,Kotlyarov A,et al.MK2 targets AUrich elements and regulates biosynthesis of tumor necrosis factor and interleukin-6 independently at different post-transcriptional levels.J Biol Chem,2002,277:3065-3068.
  • [8]Ebrahimian T,Li MW,Lemarié CA,et al.Mitogen-activated protein kinase-activated protein kinase 2 in angiotensin II-induced inflammation and hypertension:regulation of oxidative stress.Hypertension,2011,57:245-254.
  • [9]Manolio TA,Brooks LD,Collins FS.A HapMap harvest of insights into the genetics of common disease.J Clin Invest,2008,118:1590-1605.
  • [10]Loos RJ,Katzmarzyk PT,Rao DC,et al.Genotne-wide linkage scan for the metabolic syndrome in the Heritage Family Study.J Clin Endocrinol Metab,2003,88:5935-5943.
  • [11]Paeholczyk M,Ferenc T,Kowalski J.The metabolic syndrome.Part Ⅱ:its mechanisms of development and its complications.Postepy Hig Med Dosw,2008,62:543-558.
  • [12]Esposito K, Giugliano D. The metabolic syndrome and inflammation:association or causation? Nutr Metab Cardiovasc Dis,2004,14:228-232.
  • [13]Hotamisligil GS.Inflammation and metabolic disorders.Nature,2006,444:860-867.
  • [14]Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes.J Clin Invest,2005,115:1111-1119.
  • [15]Reilly MP,Rader DJ.The metabolic syndrone:more than the sum of its parts? Circulation,2003,108:1546-1551.
  • [16]Tamakoshi K,Yatsuya H,Kondo T,et al.The metabolic syndrome is associated with elevated circulating C-reactive protein in healthy reference range,a systemic low-grade inflammatory state.Int J Obes Relat Metab Disord,2003,27:443-449.
  • [17]Xydakis AM, Case CC, Jones PH, et al. Adiponectin,inflammation,and the expression of the metabolic syndrome in obese individuals:the impact of rapid weight loss through caloric restriction..J Clin Endocrinol Metab,2004,89:2697-2703.
  • [18]Bermudez EA,Rifai N,Buring J,et al.Interrelationships among circulating interleukin-6,C-reactive protein,and traditional cardiovascular risk factors in women.Arterioscler Thromb Vasc Biol,2002,22:1668-1673.
  • [19]祁燕,谢自敬,阿不力克木.乌鲁木齐市维吾尔族成年人代谢综合症流行病学调查.中国现代医学杂志,2004,14:155-156.
  • [20]Alberti KG,Zimmet P,Shaw J,et al.The metabolic syndrome:a new worldwide definition.Lancet.2005,366:1059-1062.
  • [21]祝之明.代谢综合征的诊断和治疗.中华心血管病杂志,2004,32:1163-1166.
  • [22]Després JP,Lemieux I,Bergeron J,et al.Abdominal obesity and the metabolic syndrome:contribution to global cardiometabolic risk.Arterioscler Thromb Vasc Biol,2008,28:1039-1049.
WanfangData CO.,Ltd All Rights Reserved
About WanfangData | Contact US
Healthcare Department, Fuxing Road NO.15, Haidian District Beijing, 100038 P.R.China
Tel:+86-010-58882616 Fax:+86-010-58882615 Email:yiyao@wanfangdata.com.cn