Linkage disequilibrium analyses of natriuretic peptide precursor B locus reveal risk haplotype conferring high plasma BNP levels.
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.


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+/-0.6pg/ml), 697 heterozygous carriers (35.0+/-1.1pg/ml), and 52 homozygous C-allele carriers (46.0+/-4.1pg/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.


CONCLUSIONS
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.
Takeishi
Yasuchika
Y
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, Japan. takeishi@med.id.yamagata-u.ac.jp
Toriyama
Sayumi
S
Takabatake
Noriaki
N
Shibata
Yoko
Y
Konta
Tsuneo
T
Emi
Mitsuru
M
Kato
Takeo
T
Kawata
Sumio
S
Kubota
Isao
I
D000368:Aged; D000704:Analysis of Variance; D044466:Asian People / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D020097:Natriuretic Peptide, Brain