河南新乡地区汉族群体MMPs基因启动子区5个SNPs与CHF发病风险关联性研究
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摘要
目的探讨河南新乡地区汉族群体基质金属蛋白酶基因启动子区rs2285053、rs11225395、rs225207、rs243865及rs11568818这5个单核苷酸多态性(SNPs)与心力衰竭(CHF)发病的相关性。方法知情同意情况下,采集160例CHF患者(观察组)和186例健康体检者(对照组)外周静脉血提取基因组DNA,限制性扩增片段长度多态性方法对5个SNPs进行分型,运用SHEsis软件分析数据。结果与对照组相比,MMPs基因rs2285053位点T等位基因的频率在观察组中显著降低(P<0.05);rs11225395位点的T等位基因和TT基因型频率在观察组中也显著降低(P<0.05),OR=1.966[95%CI(1.236~3.129)];而观察组中rs225207的G等位基因频率显著增加(P<0.05),OR=0.499[95%CI(0.320~3.799];rs2285053、rs11225395、rs225207组成的单体型CCG在观察组中的频率增高(P<0.05)。结论 rs11225395和rs2285053位点的等位基因T有可能降低CHF的患病风险;而rs225207位点的等位基因G及单体型CCG可能会增加CHF的患病风险。
Objective To assess the relationship between 5 SNPs including rs2285053,rs11225395,rs225207,rs243865 and rs11568818 at the promoter region of matrix metalloproteinases(MMPs) genes and the risk of chronic heart failure(CHF) in Han population from Xinxiang city of Henan province. Methods 5 SNPs sites of 160 CHF patients(observation group) and 186 healthyin dividuals(control group) were genotyped by PCR-RFLP methods. Then the data was analyzed by SHEsis software. Results The frequency of T allele of rs11225395 of patients in the observation group was significantly lower than that in the control group(P < 0. 05). The frequency of T allele and TT genotype of rs11225395 of patients in the observation group was lower than that in the control group(P < 0. 05) OR = 1. 96[95%CI(1. 236 ~ 3. 129)〗. The G allele of rs225207 of patients in the observation group was higher than that in the control group(P < 0. 05),OR = 0. 499[95%CI(0. 320 ~ 3. 799〗. The haplotype CCG consisting of rs2285053,rs11225395 and rs2285053 of patients in observation group was higher than those in the control group(P < 0. 05). Conclusion T allele of rs2285053 and rs11225395,G allele of rs225207 and the haplotype CCG may decrease the risk of CHF.
Objective To assess the relationship between 5 SNPs including rs2285053,rs11225395,rs225207,rs243865 and rs11568818 at the promoter region of matrix metalloproteinases(MMPs) genes and the risk of chronic heart failure(CHF) in Han population from Xinxiang city of Henan province. Methods 5 SNPs sites of 160 CHF patients(observation group) and 186 healthyin dividuals(control group) were genotyped by PCR-RFLP methods. Then the data was analyzed by SHEsis software. Results The frequency of T allele of rs11225395 of patients in the observation group was significantly lower than that in the control group(P < 0. 05). The frequency of T allele and TT genotype of rs11225395 of patients in the observation group was lower than that in the control group(P < 0. 05) OR = 1. 96[95%CI(1. 236 ~ 3. 129)〗. The G allele of rs225207 of patients in the observation group was higher than that in the control group(P < 0. 05),OR = 0. 499[95%CI(0. 320 ~ 3. 799〗. The haplotype CCG consisting of rs2285053,rs11225395 and rs2285053 of patients in observation group was higher than those in the control group(P < 0. 05). Conclusion T allele of rs2285053 and rs11225395,G allele of rs225207 and the haplotype CCG may decrease the risk of CHF.
引文
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[12]Rahimi Z,Zangeneh M,Rezaeyan A,et al.MMP-8 C-799T and MMP-8 C+17G polymorphisms in mild and severe preeclampsia:Association between MMP-8 C-799T with susceptibility to severe preeclampsia[J].Clin Exp Hypertens,2018,40(2):175-178.DOI:10.1080/10641963.2017.1346115.
[13]Ahram M,Mustafa E,Zaza R,et al.Differential expression and androgen regulation of microRNAs and metalloprotease 13 in breast cancer cells[J].Cell Biol Int,2017,41(12):1345-1355.DOI:10.1002/cbin.10841.
[2]Hasei J,Teramura T,Takehara T,et al.TWIST1 induces MMP3 expression through up-regulating DNA hydroxymethylation and promotes catabolic responses in human chondrocytes[J].Sci Rep,2017,7:42990.DOI:10.1038/srep42990.
[3]殷国田,赵林静,黄艳梅,等.MMP-2基因多态性与河南汉族群体慢性充血性心力衰竭的相关性[J].中国老年学杂志,2014,34(1):23-26.
[4]殷国田,张银珂,黄艳梅,等.基质金属蛋白酶-9基因多态性与河南汉族人群慢性心力衰竭的相关性[J].广东医学,2015,36(6):853-856.
[5]马圆真,刘亚静,徐光华,等.基质金属蛋白酶基因启动区3个单核苷酸多态性与河南汉族群体慢性心力衰竭遗传易感性关联研究[J].新乡医学院学报,2016(7):568-571.
[6]Dokainish H,Teo K,Zhu J,et al.Heart Failure in Africa,Asia,the Middle East and South America:The INTER-CHF study[J].Int J Cardiol,2016,204:133-141.DOI:10.1016/j.ijcard.2015.11.183.
[7]Leung M,Wong VW,Hudson M,et al.Impact of Improved Glycemic Control on Cardiac Function in Type 2Diabetes Mellitus[J].Circ Cardiovasc Imaging,2016,9(3):e003643.DOI:10.1161/CIRCIMAGING.115.003643.
[8]Teplyakov AT,Berezikova EN,Shilov SN,et al.Assessment of the role of matrix metalloproteinase-3 gene polymorphism in the development of chronic heart failure[J].Ter Arkh,2015,87(4):8-12.DOI:10.17116/terarkh20158748-12.
[9]Buraczynska M,Dragan M,Buraczynska K,et al.Matrix metalloproteinase-2(MMP-2)gene polymorphism and cardiovascular comorbidity in type 2 diabetes patients[J].J Diabetes Complicat,2015,29(6):829-833.DOI:10.1016/j.jdiacomp.2015.05.004.
[10]Vask A,GoldbergováM,IzakovicováHolláL,et al.A haplotype constituted of four MMP-2 promoter polymorphisms(-1575G/A,-1306C/T,-790T/G and-735C/T)is associated with coronary triple-vessel disease[J].Matrix Biol,2004,22(7):585-591.DOI:10.1016/j.matbio.2003.10.004.
[11]Salminen A,strm P,Metso J,et al.Matrix metalloproteinase 8 degrades apolipoprotein A-I and reduces its cholesterol efflux capacity[J].FASEB J,2015,29(4):1435-1445.DOI:10.1096/fj.14-262956.
[12]Rahimi Z,Zangeneh M,Rezaeyan A,et al.MMP-8 C-799T and MMP-8 C+17G polymorphisms in mild and severe preeclampsia:Association between MMP-8 C-799T with susceptibility to severe preeclampsia[J].Clin Exp Hypertens,2018,40(2):175-178.DOI:10.1080/10641963.2017.1346115.
[13]Ahram M,Mustafa E,Zaza R,et al.Differential expression and androgen regulation of microRNAs and metalloprotease 13 in breast cancer cells[J].Cell Biol Int,2017,41(12):1345-1355.DOI:10.1002/cbin.10841.