Sequence variation of bradykinin receptors B1 and B2 and association with hypertension.
OBJECTIVE
To identify variants in the complete genomic sequence of the two subtypes of bradykinin receptors: B1 (BDKRB1) and B2 (BDKRB2) and to examine the association of these variants with essential hypertension.


METHODS
A case-control design comparing hypertensive and normotensive individuals was used.


METHODS
A 64.4 kb genomic region containing the BDKRB1 and BDKRB2 genes was sequenced in 30 African-American individuals. A total of 282 single-nucleotide polymorphisms (SNPs) were identified. A total of 21 SNPs were genotyped in our complete cohorts of hypertensive and normotensive African-Americans (n = 218), American-Caucasians (n = 220) and Greek-Caucasians (n = 194). Pair-wise correlation coefficients were computed to assess linkage disequilibrium (LD) patterns among the SNPs. Chi-squared tests and logistic regression were used to assess association between the SNPs and hypertension status.


RESULTS
Pairwise LD demonstrated a general pattern of decline with increasing distance, which was consistent among the three groups with less LD in African-Americans. One SNP in the promoter region of BDKRB2 (rs1799722) was associated with hypertension (P = 0.044) in African-Americans. One SNP in BDKRB2 and three SNPs in BDKRB1 were associated with hypertension (P-values between 0.026 and 0.0004) in American-Caucasians. Haplotypes including those four SNPs and one SNP in B2, which results in an amino acid change, demonstrated a significant haplotype frequency difference between hypertensive and normotensive American-Caucasians (P = 0.025).


CONCLUSIONS
These results support the hypothesis that the African-American population is an older population compared with the other samples and the two bradykinin receptors may play a role in blood pressure regulation.
Cui
Jing
J
Hypertension Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Melista
Efthymia
E
Chazaro
Irmarie
I
Zhang
Yuejian
Y
Zhou
Xiaofeng
X
Manolis
Athanasios J
AJ
Baldwin
Clinton T
CT
Destefano
Anita L
AL
Gavras
Haralambos
H
D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000208:ethnology* / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D043783:Receptor, Bradykinin B1 / Q000235:genetics*; D043782:Receptor, Bradykinin B2 / Q000235:genetics*; D044465:White People / Q000235:genetics*
D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2