IGF2R基因58298A/G多态性与广西壮族人群长寿群体心血管危险因素的相关性
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摘要
目的探讨广西红水河流域长寿人群胰岛素样生长因子2受体(IGF2R)rs9456497位点多态性与心血管危险因素的关系。方法采用改良的多重高温连接酶检测反应技术(i MLDR)对该流域壮族长寿老人(长寿组,n=496)及其第一代子女(子女组,n=723)以及普通健康中老年人(对照组,n=611)进行rs9456497位点的基因分型,并分析各基因型对体质指数(BMI)、血压(SBP,DBP)、空腹血糖(FPG)及血脂指标等心血管危险因素的影响。结果长寿组GA/GG基因型明显降低SBP和DBP(P=0.016,0.033)。在男性人群中,子女组各基因型的总胆固醇(TC)水平高于长寿组和对照组相应基因型的TC水平(P均<0.05);长寿组各基因型的TG、FPG和BMI水平低于子女组和对照组相应基因型的TG、FPG和BMI水平(P均<0.05),而SBP和DBP水平则高于子女组和对照组(P均<0.05)。在女性人群中,长寿组各基因型的TG、FPG和BMI水平显著低于子女组和对照组,而SBP和DBP则高于子女组和对照组;组内比较显示,对照组GG/GA基因型的FPG明显低于AA基因型(P=0.041),其余指标在各组的基因型间差异无显著性。血脂分层发现,总体人群及对照组等位基因G的频率在血脂异常亚组中明显升高,即该突变具有使血脂异常率升高的趋势;GA/GG基因型明显降低长寿组血脂正常亚组的TC和SBP水平,降低对照组血脂正常亚组的DBP及血脂异常亚组的低密度脂蛋白胆固醇(LDLC)水平。结论 IGF2R rs9456497多态总体上与长寿群体心血管危险因素有一定的关系,但作用有限,而且还受到不同性别及不同血脂状态的影响。
Aim To explore the possible association between insulin like growth factor Ⅱ receptor( IGF2R)rs9456497 polymorphism and cardiovascular risks in a long-lived population residing Guangxi Hongshui River basin.Methods IGF2 R rs9456497 polymorphism was genotyped by i MLDR technique for 496 Zhuang long-lived individuals( long-living group) and their offspring( offspring group,n= 723) and matched healthy controls( control group,n = 611)living in Hongshui River basin. Association analysis were then conducted among genotypes and blood pressure,body mass index( BMI) and serum lipid levels. Results Overall,no significant difference was detected among genotypes in each group except that the mutant genotype( GA / GG) tended to reduce the SBP and DBP levels( P = 0.016 and 0.033,respectively) in longevity group. However,after sex stratification,in males,the total cholesterol( TC) level of each genotype in offspring was elevated as compared with relevant genotype in longevity group and control group( P<0.05 for each); the triglyceride( TG),fasting plasma glucose( FPG) and BMI levels of each genotype in longevity group were lower while SBP and DBP levels were higher than that of the relevant genotype in offspring and controls( P< 0.05 for each). In females,longevity group tended to display lower TG,FPG and BMI but higher SBP and DBP levels than offspring and controls as in males; intragroup comparison showed that the FPG level of GG / GA genotype was significantly lower than that of AA genotype( P = 0.041) in controls while other parameters did not differ across genotypes in each group( P>0.05 for all). After stratified by lipid status,the frequency of G allele was markedly increased in the dyslipidemic subgroup in the combined population and controls which might imply that A >G mutation on rs9456497 tend to increase the rate of dyslipidemia; G genotype( GA / GG) greatly lowered the TC and SBP levels in the logevous normolipidemic subgroup,lowered the DBP level of normolipidemic subgroup and the low density lipoprotein cholesterol( LDLC) of the dyslipidemic group but increased the TC level of normolipidemic subgroup in controls. Conclusion IGF2 R rs9456497 polymorphism may correlate with the cardiovascular risks to some extent,but its effects on the modulation of these risk factors seem limited,which may be influenced by sex and lipid status.
Aim To explore the possible association between insulin like growth factor Ⅱ receptor( IGF2R)rs9456497 polymorphism and cardiovascular risks in a long-lived population residing Guangxi Hongshui River basin.Methods IGF2 R rs9456497 polymorphism was genotyped by i MLDR technique for 496 Zhuang long-lived individuals( long-living group) and their offspring( offspring group,n= 723) and matched healthy controls( control group,n = 611)living in Hongshui River basin. Association analysis were then conducted among genotypes and blood pressure,body mass index( BMI) and serum lipid levels. Results Overall,no significant difference was detected among genotypes in each group except that the mutant genotype( GA / GG) tended to reduce the SBP and DBP levels( P = 0.016 and 0.033,respectively) in longevity group. However,after sex stratification,in males,the total cholesterol( TC) level of each genotype in offspring was elevated as compared with relevant genotype in longevity group and control group( P<0.05 for each); the triglyceride( TG),fasting plasma glucose( FPG) and BMI levels of each genotype in longevity group were lower while SBP and DBP levels were higher than that of the relevant genotype in offspring and controls( P< 0.05 for each). In females,longevity group tended to display lower TG,FPG and BMI but higher SBP and DBP levels than offspring and controls as in males; intragroup comparison showed that the FPG level of GG / GA genotype was significantly lower than that of AA genotype( P = 0.041) in controls while other parameters did not differ across genotypes in each group( P>0.05 for all). After stratified by lipid status,the frequency of G allele was markedly increased in the dyslipidemic subgroup in the combined population and controls which might imply that A >G mutation on rs9456497 tend to increase the rate of dyslipidemia; G genotype( GA / GG) greatly lowered the TC and SBP levels in the logevous normolipidemic subgroup,lowered the DBP level of normolipidemic subgroup and the low density lipoprotein cholesterol( LDLC) of the dyslipidemic group but increased the TC level of normolipidemic subgroup in controls. Conclusion IGF2 R rs9456497 polymorphism may correlate with the cardiovascular risks to some extent,but its effects on the modulation of these risk factors seem limited,which may be influenced by sex and lipid status.
引文
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[2]Gemma A,Hosoya Y,Uematsu K,et al.Mutation analysis of the gene encoding the human mannose 6-phosphate/insulin-like growth factor 2 receptor(M6P/IGF2R)in human cell lines resistant to growth inhibition by transforming growth factor beta(1)(TGF-beta(1))[J].Lung Cancer,2000,30(2):91-98.
[3]Akanji AO,Smith RJ.The insulin-like growth factor system,metabolic syndrome,and cardiovascular disease risk[J].Metab Syndr Relat Disord,2012,10(1):3-13.
[4]Gholamhosseini S,Nematipour E,Djazayery A,et al.ω-3fatty acid differentially modulated serum levels of IGF1 and IGFBP3 in men with CVD:a randomized,double-blind placebo-controlled study[J].Nutrition,2015,31(3):480-484.
[5]Hoyo C,Murphy SK,Schildkraut JM,et al.IGF2R genetic variants,circulating IGF2 concentrations and colon cancer risk in African Americans and Whites[J].Dis Markers,2012,32(2):133-141.
[6]Soerensen M,Dato S,Tan Q,et al.Human longevity and variation in GH/IGF-1/insulin signaling,DNA damage signaling and repair and pro/antioxidant pathway genes:cross sectional and longitudinal studies[J].Exp Gerontol,2012,47(5):379-387.
[7]Bergman D,Halje M,Nordin M,et al.Insulin-like growth factor 2 in development and disease:a mini-review[J].Gerontology,2013,59(3):240-249.
[8]Tsai KH,Lee NH,Chen GY,et al.Dung-shen(Codonopsis pilosula)attenuated the cardiac-impaired insulin-like growth factor II receptor pathway on myocardial cells[J].Food Chem,2013,138(2-3):1 856-867.
[9]Chanprasertyothin S,Jongjaroenprasert W,Ongphiphadhanakul B.The association of soluble IGF2R and IGF2R gene polymorphism with type 2 diabetes[J].J Diabetes Res,2015,2015:216 383.
[10]Lee SD,Chu CH,Huang EJ,et al.Roles of insulin-like growth factor II in cardiomyoblast apoptosis and in hypertensive rat heart with abdominal aorta ligation[J].Am J Physiol Endocrinol Metab,2006,291(2):E306-314.