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中老年患者KLOTHO基因G-395A多态性与心力衰竭和心肌纤维化的相关性

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2015年第3期
页码:
278-282,297
栏目:
临床研究
出版日期:
2015-01-11

文章信息/Info

Title:
Correlation of polymorphisms of KLOTHO gene G-395A and heart failure and myocardial fibrosis in middle-aged and elderly patients
作者:
罗明雄1魏 玲2陈小丹1
(1.苏州市吴中人民医院心内科,江苏 苏州 215100;
2.成都军区昆明总医院老年重症救治中心,云南 昆明 650032)
Author(s):
LUO Ming-xiong1 WEI Ling2 CHEN Xiao-dan1
(1.Department of Cardiology, Wuzhong People’s Hospital, Suzhou 215100, Jiangsu, China;
2.ICU for Senior Patients, Kunming General Hospital, Chengdu Military Area Command, Kunming 650032, Yunnan, China)
关键词:
KLOTHO基因单核苷酸多态性心力衰竭心肌纤维化
Keywords:
KLOTHO gene single nucleotide polymorphisms heart failure myocardial fibrosis
分类号:
R541.6;R542.23
DOI:
-
文献标识码:
A
摘要:
目的:观察分析中老年患者KLOTHO基因G-395A多态性与心力衰竭(HF)和心肌纤维化的相关性。方法:随机选择无血缘关系的中老年患者212例, 提取外周血白细胞基因组DNA, 采用单一等位基因特异性引物PCR技术检测KLOTHO基因G-395A位点多态性,分析其在不同年龄组的分布是否有统计学意义;并把中老年患者分为HF组和非HF组,分析KLOTHO基因G-395A多态性与HF的相关性及与HF各严重程度分级的相关性;同时采用ELISA方法检测上述212例患者血液标本血清中Ⅰ型前胶原羧基端肽(PⅠCP),Ⅲ型前胶原氨基端肽(PⅢNP)的浓度,分析KLOTHO基因G-395A多态性与心肌纤维化的相关性。结果:①G-395A位点存在多态性,出现3种基因型。②该位点基因型在中老年患者中频率分布总体上没有显著差异(χ2=12.159 P=0.121);进一步分析各年龄组两两之间与基因型频率分布均无显著差异。③中老年患者KLOTHO基因G-395A多态性与HF发病危险性呈显著相关(χ2=23.634 P=0.00);进一步分析显示AG是GG易患HF的1.991倍;AA是GG易患HF的1.527倍;GG可能对HF是保护因素。而与HF分级差异比较没有统计学意义(P=0.202)。④Ⅰ、Ⅲ型胶原浓度及Ⅰ/Ⅲ比值与中老年患者G-395A的3种基因型比较没有显著差异,与基因型不相关。结论:在中老年患者中, KLOTHO基因启动子区G-395A呈现3种多态性,这3种多态性与HF发病危险性呈显著相关, 携带A等位基因发生HF的危险性明显高于携带G等位基因的患者,GG可能对HF是保护因素;而与HF分级差异比较及与心肌纤维化程度比较没有统计学意义。
Abstract:
AIM:To analyze the correlation of polymorphisms of KLOTHO gene G-395A and heart failure and myocardial fibrosis in middle-aged and elderly patients. METHODS: Two hundred and twelve non-sanguineously related middle-aged and elderly patients were randomly selected and peripheral blood leucocyte genome DNA was extracted. KLOTHO gene G-395-A polymorphic loci were detected using the single allele-specific primer PCR technique and the statistical significance of the distribution in different age groups was analyzed. At the same time, the blood concentrations of serum I carboxy-terminal peptide of procollagen (PICP) and III procollagen amino-terminal peptide (PIIINP) were detected using ELISA. The correlation of KLOTHO gene G-395A polymorphisms with heart failure and myocardial fibrosis was analyzed. RESULTS: G-395-A polymorphism loci presented three genotypes. No significant difference was seen in the site of genotype frequency distribution in middle-aged and elderly patients (χ2=12.159 P=0.121). Further analysis between any two age groups and genotype frequency distribution found no significant difference. KLOTHO gene G-395-A polymorphism was significantly associated with heart disease risks in middle-aged and elderly patients (χ2 = 23.634 P=0.00). AG was found 1.991 times more susceptible to heart failure than GG and AA was 1.527 times more susceptible to heart failure than GG. GG might be a protective factor for heart failure. No statistical difference was found between heart failure classifications and myocardial fibrosis degrees (P=0.202). No significant difference was found in the concentrations of collagen type I and III and in I/III concentration ratios compared with the three genotypes of G-395-A in middle-aged and elderly patients and were not related to genotypes. CONCLUSION: In middle-aged and elderly patients, KLOTHO gene promoter region G-395-A presents three types of polymorphism and the three polymorphisms are all significantly associated with the onset of heart failure. The risk of heart failure in patients with A alleles is significantly higher than that in patients with G allele and GG may be a protective factor for heart failure. The difference between the classifications of heart failure and the degrees of myocardial fibrosis are not statistically significant.

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备注/Memo

备注/Memo:
收稿日期:2014-05-08.
作者简介:罗明雄,主治医师,硕士Email:lmx750104@163.com
更新日期/Last Update: 2015-02-03