Linkage disequilibrium analyses of natriuretic peptide precursor B locus reveal risk haplotype conferring high plasma BNP levels
Linkage disequilibrium analyses of natriuretic peptide precursor B locus reveal risk haplotype conferring high plasma BNP levels
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DOI：
10.1016/j.bbrc.2007.08.028
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发表时间：
2007-10-19
影响因子：
3.1
通讯作者：
Kubota, Isao
中科院分区：
文献类型：
--
作者：
Takeishi, Yasuchika;Torlyama, Sayumi;Kubota, Isao
背景资料。脑利钠肽(BNP)已广泛应用于慢性心力衰竭(CHF)的诊断和预后评估。在本研究中，我们对2970名日本成年人进行了利钠肽前体B(NPPB)基因周围的单核苷酸多态(SNPs)与血浆BNP水平的相关性研究。方法和结果。NPPB基因SNP与血浆BNP的关联分析显示，NPPB基因周围的8个SNP与血浆BNP水平显著相关。例如，对于SNP rs198389(T-381C)，在三种基因类型中，即2189名纯合子T等位基因携带者(BNP26.4+/-0.6pg/ml)、697名杂合携带者(35.0Pg/ml)和52名纯合子C等位基因携带者(46.0Pg/ml)的血浆BNP水平表明，少量C等位基因对血浆BNP水平的升高具有共显性作用(P<0.0001)。对8个SNPs的连锁不平衡分析表明，该区域由2个5‘长和3’长的连锁不平衡区块组成。基于单倍型的关联分析表明，血浆BNP水平与主要LD区块的单倍型-1和-2密切相关。结论。这些结果提示，以危险单倍型定义为代表的NPPB基因的遗传变异可能是血浆BNP水平的重要决定因素。(C)2007 Elsevier Inc.保留所有权利。
Background. Brain natriuretic peptide (BNP) has been widely used for the diagnosis and prognostic evaluation of chronic heart failure (CHF). In the present study, we performed association study of single nucleotide polymorphisms (SNPs) surrounding the natriuretic peptide precursor B (NPPB) gene with plasma BNP levels in 2970 adult Japanese. Methods and Results. Association analysis between SNPs of the NPPB gene and plasma BNP revealed significant associations of the 8 SNPs surrounding the entire NPPB gene with plasma BNP levels. For instance, as to SNP rs198389 (T-381C), plasma BNP levels among the three genotypic categories, i.e., 2189 homozygous T-allele carriers (BNP 26.4 +/- 0.6 pg/ml), 697 heterozygous carriers (35.0 +/- 1.1 pg/ml), and 52 homozygous C-allele carriers (46.0 +/- 4.1 pg/ml) indicated a co-dominant effect of the minor C- allele on elevating plasma BNP levels (P < 0.0001). Linkage disequilibrium (LD) analysis among the 8 SNPs revealed that the region consisted of two, 5 ' major and 3 ' minor, LD blocks. Haplotype-based association analysis demonstrated that plasma BNP levels were associated closely with the haplotypes-1 and -2 of the major LD block. Conclusion. These results suggest that genetic variation at the primary locus NPPB gene, represented by definition of risk haplotypes, may be an important determinant of plasma BNP levels. (c) 2007 Elsevier Inc. All rights reserved.