维生素D受体基因多态性与北京地区老年男性原发性高血压的相关性
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摘要
目的探讨维生素D受体(vitamin D receptor,VDR)基因多态性与北京地区汉族老年男性原发性高血压(essential hypertension,EH)的相关性。方法选择2008年4月～2013年7月解放军总医院收治的老年男性EH患者228例(EH组),另选择同期老年男性健康体检者184例(对照组),采用PCR-RFLP检测VDR基因Fok I、Bsm I、Apa I及Taq I位点基因型和等位基因频率,同时与相关临床指标进行比较。结果 EH组Fok I C等位基因频率较对照组明显升高(72. 4%vs 66. 0%,P=0. 049);在隐性模型下,EH组CC+CT基因型较对照组显著升高(χ~2=4. 320,OR=2. 076,95%CI:1. 030～4. 182,P=0. 038)。EH组与对照组Bsm I、Apa I及Taq I基因型及基因频率比较,差异无统计学意义(P> 0. 05)。非条件logistic回归分析显示,Fok I基因CC+CT基因型是老年男性EH的危险因素(OR=2. 054,95%CI:1. 003～4. 204,P=0. 049)。结论 VDR基因Fok I位点多态性可能是老年男性EH的危险因素,而Bsm I、Apa I及Taq I多态性与老年男性EH不相关。
Objective To study the relationship between vitamin D receptor( VDR) gene polymorphism and Beijing elderly male essential hypertension( EH) patients. Methods Two hundred and twenty-eight elderly male EH patients served as an EH group and 184 healthy elderly males undergoing physical examination served as a control group. The FokI,BsmI,ApaI,TaqI allelic gene polymorphisms were detected by PCR-RFLP and compared with the related clinical parameters. Results The detection rate of FokI C allelic gene polymorphism was significantly higher in EH group than in control group( 72. 4% vs 66. 0%,P= 0. 049). The number of CC + CT genotypes in a recessive model was significantly greater in EH group than in control group( χ~2= 4. 320,OR = 2. 076,95% CI: 1. 030-4. 182,P = 0. 038). No significant difference was found in genotypes and polymorphisms of BsmI,ApaI and TaqI between the two groups( P> 0. 05). Unconditional logistic regression analysis showed that CC + CT genotype of FokI gene was a risk factor for EH in elderly male patients( OR = 2. 054,95% CI: 1. 003-4. 204,P = 0. 049). Conclusion VDR gene polymorphism at FokI is a risk factor for EH in elderly male patients while BsmI,ApaI and TaqI polymorphisms are not related with EH in elderly male patients.
Objective To study the relationship between vitamin D receptor( VDR) gene polymorphism and Beijing elderly male essential hypertension( EH) patients. Methods Two hundred and twenty-eight elderly male EH patients served as an EH group and 184 healthy elderly males undergoing physical examination served as a control group. The FokI,BsmI,ApaI,TaqI allelic gene polymorphisms were detected by PCR-RFLP and compared with the related clinical parameters. Results The detection rate of FokI C allelic gene polymorphism was significantly higher in EH group than in control group( 72. 4% vs 66. 0%,P= 0. 049). The number of CC + CT genotypes in a recessive model was significantly greater in EH group than in control group( χ~2= 4. 320,OR = 2. 076,95% CI: 1. 030-4. 182,P = 0. 038). No significant difference was found in genotypes and polymorphisms of BsmI,ApaI and TaqI between the two groups( P> 0. 05). Unconditional logistic regression analysis showed that CC + CT genotype of FokI gene was a risk factor for EH in elderly male patients( OR = 2. 054,95% CI: 1. 003-4. 204,P = 0. 049). Conclusion VDR gene polymorphism at FokI is a risk factor for EH in elderly male patients while BsmI,ApaI and TaqI polymorphisms are not related with EH in elderly male patients.
引文
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[20] Zhou TB,Jiang ZP,Lin ZJ,et al. Association of vitamin D receptor gene polymorphism with the risk of systemic lupus erythematosus[J]. J Recept Signal Transduct Res,2015,35(1):8-14.DOI:10. 3109/10799893. 2014. 922577.
[21] Zhao Y,Liao S,He J,et al. Association of vitamin D receptor gene polymorphisms with metabolic syndrome:a case-control design of population-based cross-sectional study in North China[J]. Lipids Health Dis,2014,13:129. DOI:10. 1186/1476-511X-13-129.
[22] La Marra F,Stinco G,Buligan C,et al. Immunohistochemical evaluation of vitamin D receptor(VDR)expression in cutaneous melanoma tissues and four VDR gene polymorphisms[J]. Cancer Biol Med,2017,14(2):162-175. DOI:10. 20892/j. issn.2095-3941. 2017. 0020.
[23] Jia J,Shen C,Mao L,et al. Vitamin D receptor genetic polymorphism is significantly associated with decreased risk of hypertension in a Chinese Han population[J]. J Clin Hypertens(Greenwich),2014,16(9):634-639. DOI:10. 1111/jch. 12386.
[24] Vaidya A,Sun B,Forman JP,et al. The Fok1 vitamin D receptor gene polymorphism is associated with plasma renin activity in Caucasians[J]. Clin Endocrinol(Oxf),2011,74(6):783-790.DOI:10. 1111/j. 1365-2265. 2011. 03991. x.
[25] Batacchi Z,Robinson-Cohen C,Hoofnagle AN,et al. Effects of vitamin D2 supplementation on vitamin D3 metabolism in health and CKD[J]. Clin J Am Soc Nephrol,2017,12(9):1498-1506.DOI:10. 2215/CJN. 00530117.
[2] Wang L,Chu A,Buring JE,et al. Buring,et al. Common genetic variations in the vitamin D pathway in relation to blood pressure[J]. Am J Hypertens,2014,27(11):1387-1395. DOI:10.1093/ajh/hpu049.
[3] Carbone F,Mach F,Vuilleumier N,et al. Potential pathophysiological role for the vitamin D deficiency in essential hypertension[J]. World J Cardiol,2014,6(5):260-276. DOI:10. 4330/wjc. v6. i5. 260.
[4] Mc Mullan CJ,Borgi L,Curhan GC,et al. The effect of vitamin D on renin-angiotensin system activation and blood pressure:a randomized control trial[J]. J Hypertens,2017,35(4):822-829.DOI:10. 1097/HJH. 0000000000001220.
[5] Haussler MR,Whitfield GK,Kaneko I,et al. Molecular mechanisms of vitamin D action[J]. Calcif Tissue Int,2013,92(2):77-98. DOI:10. 1007/s00223-012-9619-0.
[6] Christakos S,Dhawan P,Verstuyf A,et al. Vitamin D:metabolism,molecular mechanism of action,and pleiotropic effects[J].Physiol Rev,2016,96(1):365-408. DOI:10. 1152/physrev.00014. 2015.
[7] Hansen JG,Tang W,Hootman KC,et al. Genetic and environmental factors are associated with serum 25-hydroxyvitamin D concentrations in older African Americans[J]. J Nutr,2015,145(4):799-805. DOI:10. 3945/jn. 114. 202093.
[8] Ndiaye NC,Said el S,Stathopoulou MG,et al. Epistatic study reveals two genetic interactions in blood pressure regulation[J].BMC Med Genet,2013,14:2. DOI:10. 1186/1471-2350-14-2.
[9] Wang L,Ma J,Manson JE,et al. A prospective study of plasma vitamin D metabolites,vitamin D receptor gene polymorphisms,and risk of hypertension in men[J]. Eur J Nutr,2013,52(7):1771-1779. DOI:10. 1007/s00394-012-0480-8.
[10] Swapna N,Vamsi UM,Usha G,et al. Risk conferred by Fok I polymorphism of vitamin D receptor(VDR)gene for essential hypertension[J]. Indian J Hum Genet,2011,17(3):201-206.DOI:10. 4103/0971-6866. 92104.
[11] Maalmi H,Sassi,FH,Berraies A,et al. Association of vitamin D receptor gene polymorphisms with susceptibility to asthma in Tunisian children:a case control study[J]. Hum Immunol,2013,74(2):234-240. DOI:10. 1016/j. humimm. 2012. 11. 005.
[12] Zhu W,Li J,Sun X,et al. Association of G-protein beta3 subunit gene C825T polymorphism with cardiac and cerebrovascular events in Chinese hypertensive patients[J]. Clin Exp Hypertens,2017,39(1):80-84. DOI:10. 1080/10641963. 2016.1210621.
[13]郑刚.高血压临床研究新进展[J].中华老年心脑血管病杂志,2018,20(6):651-655. DOI:10. 3969/j. issn. 1009-0126.2018. 06. 025.
[14] Santoro D,Caccamo D,Lucisano S,et al. Interplay of vitamin D,erythropoiesis,and the renin-angiotensin system[J]. Biomed Res Int,2015,2015:145828. DOI:10. 1155/2015/145828.
[15] Legarth C,Grimm D,Wehland M,et al. The impact of vitamin D in the treatment of essential hypertension[J]. Int J Mol Sci,2018,19(2):E455. DOI:10. 3390/ijms19020455.
[16] Belen E,爦ahin i,Güng9r B,et al. Assessment of 25-hyd-roxyvitamin D levels in patients with resistant hypertension[J]. Med Princ Pract,2015,25(1):25-30. DOI:10. 1159/000437227.
[17] Qi D,Nie XL,Wu S,et al. Vitamin D and hypertension:prospective study and meta-analysis[J]. PLo S One,2017,12(3):e0174298. DOI:10. 1371/journal. pone. 0174298.
[18] Abbasi F,Feldman D,Caulfield MP,et al. Relationship among25-hydroxyvitamin D concentrations,insulin action,and cardiovascular disease risk in patients with essential hypertension[J].Am J Hypertens,2015,28(2):266-272. DOI:10. 1093/ajh/hpu136.
[19]孙芳,苗懿德,褚琳,等.老年男性高血压患者夜间脉压指数与血清25羟维生素D3水平的关系[J].中华老年心脑血管病杂志,2015,17(1):25-28. DOI:10. 3969/j. issn. 1009-0126. 2015. 01. 007.
[20] Zhou TB,Jiang ZP,Lin ZJ,et al. Association of vitamin D receptor gene polymorphism with the risk of systemic lupus erythematosus[J]. J Recept Signal Transduct Res,2015,35(1):8-14.DOI:10. 3109/10799893. 2014. 922577.
[21] Zhao Y,Liao S,He J,et al. Association of vitamin D receptor gene polymorphisms with metabolic syndrome:a case-control design of population-based cross-sectional study in North China[J]. Lipids Health Dis,2014,13:129. DOI:10. 1186/1476-511X-13-129.
[22] La Marra F,Stinco G,Buligan C,et al. Immunohistochemical evaluation of vitamin D receptor(VDR)expression in cutaneous melanoma tissues and four VDR gene polymorphisms[J]. Cancer Biol Med,2017,14(2):162-175. DOI:10. 20892/j. issn.2095-3941. 2017. 0020.
[23] Jia J,Shen C,Mao L,et al. Vitamin D receptor genetic polymorphism is significantly associated with decreased risk of hypertension in a Chinese Han population[J]. J Clin Hypertens(Greenwich),2014,16(9):634-639. DOI:10. 1111/jch. 12386.
[24] Vaidya A,Sun B,Forman JP,et al. The Fok1 vitamin D receptor gene polymorphism is associated with plasma renin activity in Caucasians[J]. Clin Endocrinol(Oxf),2011,74(6):783-790.DOI:10. 1111/j. 1365-2265. 2011. 03991. x.
[25] Batacchi Z,Robinson-Cohen C,Hoofnagle AN,et al. Effects of vitamin D2 supplementation on vitamin D3 metabolism in health and CKD[J]. Clin J Am Soc Nephrol,2017,12(9):1498-1506.DOI:10. 2215/CJN. 00530117.