164Ile allele in the beta2-Adrenergic receptor gene is associated with risk of elevated blood pressure in women. The Copenhagen City Heart Study.
OBJECTIVE
Since beta2-adrenergic receptors are important regulators of blood pressure, genetic variation in this receptor could explain risk of elevated blood pressure in selected individuals. We tested the hypothesis that Gly16Arg, Gln27Glu, and Thr164Ile in the beta2-adrenergic receptor gene associated with elevated blood pressure.


METHODS
We genotyped 9185 individuals from the adult Danish general population.


RESULTS
Allele frequencies of 16Arg, 27Glu, and 164Ile were 0.38, 0.44, and 0.01, respectively. Among women never treated with antihypertensive medication those heterozygous for Thr164Ile versus non-carriers had increased diastolic blood pressure (P=0.02). Women heterozygous for Thr164Ile versus non-carriers had an odds ratio for elevated blood pressure of 1.93 (95% CI: 1.30-2.86). Finally, women double heterozygous for Thr164Ile and Gln27Glu or Gly16Arg versus non-carriers at all 3 loci had an odds ratio for elevated blood pressure of 2.49 (1.28-4.85) or 3.19 (1.46-6.97). In men, blood pressure was not influenced by this genetic variation.


CONCLUSIONS
In women Thr164Ile heterozygosity is associated with increased diastolic blood pressure, and represent a risk factor for elevated blood pressure in women in the general population. This was most pronounced in those women also heterozygous for Gln27Glu or Gly16Arg.
Sethi
Amar A
AA
Department of Clinical Biochemistry, Herlev University Hospital, Herlev, Denmark.
Tybjaerg-Hansen
Anne
A
Jensen
Gorm B
GB
Nordestgaard
Børge G
BG
D000483:Alleles; D001120:Arginine / Q000737:chemistry; D001794:Blood Pressure; D015992:Body Mass Index; D003718:Denmark; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D018698:Glutamic Acid / Q000737:chemistry; D005973:Glutamine / Q000737:chemistry; D005998:Glycine / Q000737:chemistry; D006239:Haplotypes; D006339:Heart Rate; D006579:Heterozygote; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D007532:Isoleucine / Q000737:chemistry*; D015810:Linkage Disequilibrium; D008297:Male; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012306:Risk; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D012737:Sex Factors; D013997:Time Factors
D018343:Receptors, Adrenergic, beta-2; D007532:Isoleucine; D005973:Glutamine; D018698:Glutamic Acid; D001120:Arginine; D005998:Glycine