ADRB2基因SNPs与新疆哈萨克族人左室肥厚关系的研究
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摘要
目的探讨ADRB2基因+46A/G、+79G/C、+491C/T 3个SNPs与新疆哈萨克族人LVH的关系。方法采用整群随机抽样的方法,以生活在新疆塔城地区和丰县、伊犁地区新源县、阿勒泰地区福海县和富蕴县的30岁以上的定居和半定居的哈萨克族人群为研究对象,进行标准化的现场流行病学问卷调查、体格检查,收集表型资料和血标本。将入选对象根据心电图检测结果分为左室肥厚(LVH)组和非左室肥厚(NLVH)组。LVH的诊断标准按照心电图诊断标准,采用电压诊断法和Romhilt计分系统。高血压的诊断按照2005年中国高血压防治指南的诊断标准,收缩压均值≥140mmHg和/或舒张压均值≥90mmHg,以及正在服用降压药物者。排除其他疾病和原因引起的继发性高血压、严重肝肾疾病及正在服用避孕药者。用低渗溶血法破裂红细胞,采用蛋白酶K消化,饱和酚/氯仿抽提法提取白细胞DNA。采用聚合酶链反应—限制性片段长度多态性进行不同SNPs的基因分型。应用SPSS13.0统计软件进行常规统计学处理。两位点间等位基因配对连锁分析及多个变异位点的单体型分析采用SNPAlyze软件。结果(1)在扣除了年龄、平均收缩压、平均舒张压、性别、体重指数对左室肥厚的影响的前提下,未发现+46A/G、+79G/C、+491C/T与哈萨克族人LVH的相关关系。(2)在以性别作为亚变量的分析结果中,我们发现+46A/G与哈萨克族男性LVH相关,而+79G/C、+491C/T在不同性别的LVH中无差异。(3)不同SNPs间的配对连锁不平衡分析结果显示,+46A/G、+79G/C、+491C/T各位点两两之间并不存在有统计学意义的连锁不平衡关系。(4)单体型分析结果发现,研究人群ADRB2基因+46A/G、+79G/C、+491C/T 3个SNPs构成了4种主要的单体型,各单体型频率在LVH、NLVH两组中的分布不存在有统计学意义的差异。结论ADRB2基因+46A/G变异可能与新疆哈萨克族男性LVH有关,GG基因型可以降低LVH发生的易患性;ADRB2基因+79G/C、+491C/T变异可能与新疆哈萨克族LVH的发生不相关。
Objective It is well known that sympathetic nervous system play a key role in myocardium reconstruction. The aim of this study was to investigate the association of +46A/G、+79G/C、+491C/T single nucleotide polymorphisms (SNPs) ofβ2-Adrenergic receptor gene (ADRB2) with left ventricular hypertroph (LVH) in Kazak of xinjiang. Methods The study subjects were selected randomly from Xinjiang Kazakhs who lived in pasture area of Hefen,Fuhai and Fuyun county . After questionnaire and physical examination,All subjects were divided into two groups according to absence or presence of LVH determined by the electrocardio–graphy criteria and the Romhilt-Estespoint-score system. Finally,more than 370 subjects were recruited in our study. The index of hypertensive subjects were selected on the basis of the following criteria:1)systolic blood pressure≥140mmHg and/or diastolic blood pressure≥90mmHg 2)Free of secondary hypertension due to renal insufficiency or diabetes mellitus. Genomic DNA were conventionally extracted from the peripheral blood leukocytes by proteinase K digestion of nuclei. Phenol extraction was followed by ethanol precipitation of the DNA. We measured their ADRB2 gene +46 A/G、+79G/C、+491C/T polymorphisms by PCR-RFLP method and tested the association of the polymorphisms and haplotype with LVH. Statistical analyses were performed with SPSS,version 13.0. A P vale of < 0.05 was considered statistically significant. Differences in the genotypes and Allele frequencies between groups were determined withχ2 procedure. Group mean values were compared with the use of the t or F test procedure. Estimation of haplotypes frequency and analysis of Linkage Disequilibrium were performed with SNPAlyze softwares. Results (1) We confirmed that +46 A/G、+79G/C、+491C/T genetic polymorphisms are also exist in Kazakans. All of genotype distributions of the three polymorphisms were in Hardy-Weinberg equilibrium. (2) The distribution of all genotypic and allelic frequencies had no significant difference between LVH and NLVH groups (P>0.05);(3) When to analyze the tendency in frequencies of genotypes and alleles of +79G/C、+491C/T according to gender,it was still not found significant differences in LVH and NLVH (P>0.05). However,we found a significant difference of genotypes and alleles frequencies on +46 A/G between LVH and NLVH in male (P<0.05). (4) Pair wise LD analysis found there were no significant linkage disequilibrium in three SNPs. (5) 4 haplotypes were observed in our population,and we found 11 haplotypes were higher than 1%,which could explain almost 100% chromosomes. The most common haplotype was 46G-79A-491C (41.18%),next was 46G-79G-491C (33.65%). (6) There were no significant difference of all haplotypic frequencies between LVH and NLVH groups. Conclusion Our study suggest that the +46 A/G variants of ADRB2 gene may be association with LVH, and the GG genotype might be the protective factor of LVH in males of Kazakh population. Neither +79G/C nor +491C/T polymorphisms might be associated with LVH of Xinjiang Kazakhs. There were no significant cooperative influence between the three SNPs of ADRB2 gene and the development of LVH of Kazakh population.
Objective It is well known that sympathetic nervous system play a key role in myocardium reconstruction. The aim of this study was to investigate the association of +46A/G、+79G/C、+491C/T single nucleotide polymorphisms (SNPs) ofβ2-Adrenergic receptor gene (ADRB2) with left ventricular hypertroph (LVH) in Kazak of xinjiang. Methods The study subjects were selected randomly from Xinjiang Kazakhs who lived in pasture area of Hefen,Fuhai and Fuyun county . After questionnaire and physical examination,All subjects were divided into two groups according to absence or presence of LVH determined by the electrocardio–graphy criteria and the Romhilt-Estespoint-score system. Finally,more than 370 subjects were recruited in our study. The index of hypertensive subjects were selected on the basis of the following criteria:1)systolic blood pressure≥140mmHg and/or diastolic blood pressure≥90mmHg 2)Free of secondary hypertension due to renal insufficiency or diabetes mellitus. Genomic DNA were conventionally extracted from the peripheral blood leukocytes by proteinase K digestion of nuclei. Phenol extraction was followed by ethanol precipitation of the DNA. We measured their ADRB2 gene +46 A/G、+79G/C、+491C/T polymorphisms by PCR-RFLP method and tested the association of the polymorphisms and haplotype with LVH. Statistical analyses were performed with SPSS,version 13.0. A P vale of < 0.05 was considered statistically significant. Differences in the genotypes and Allele frequencies between groups were determined withχ2 procedure. Group mean values were compared with the use of the t or F test procedure. Estimation of haplotypes frequency and analysis of Linkage Disequilibrium were performed with SNPAlyze softwares. Results (1) We confirmed that +46 A/G、+79G/C、+491C/T genetic polymorphisms are also exist in Kazakans. All of genotype distributions of the three polymorphisms were in Hardy-Weinberg equilibrium. (2) The distribution of all genotypic and allelic frequencies had no significant difference between LVH and NLVH groups (P>0.05);(3) When to analyze the tendency in frequencies of genotypes and alleles of +79G/C、+491C/T according to gender,it was still not found significant differences in LVH and NLVH (P>0.05). However,we found a significant difference of genotypes and alleles frequencies on +46 A/G between LVH and NLVH in male (P<0.05). (4) Pair wise LD analysis found there were no significant linkage disequilibrium in three SNPs. (5) 4 haplotypes were observed in our population,and we found 11 haplotypes were higher than 1%,which could explain almost 100% chromosomes. The most common haplotype was 46G-79A-491C (41.18%),next was 46G-79G-491C (33.65%). (6) There were no significant difference of all haplotypic frequencies between LVH and NLVH groups. Conclusion Our study suggest that the +46 A/G variants of ADRB2 gene may be association with LVH, and the GG genotype might be the protective factor of LVH in males of Kazakh population. Neither +79G/C nor +491C/T polymorphisms might be associated with LVH of Xinjiang Kazakhs. There were no significant cooperative influence between the three SNPs of ADRB2 gene and the development of LVH of Kazakh population.
引文
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