β2 -adrenergic receptor Thr164IIe polymorphism, blood pressure and ischaemic heart disease in 66 750 individuals.

Thomsen M, Dahl M, Tybj ae rg-Hansen A, Nordestgaard BG (Copenhagen University Hospital, Copenhagen; University of Copenhagen, Copenhagen, Denmark). beta 2-adrenergic receptor Thr164IIe polymorphism, blood pressure and ischaemic heart disease in 66 750 individuals. J Intern Med 2012; 271: 305314. Objectives. The beta(2)- adrenergic receptor (ADRB2) is locatedonsmoothmuscle cellsandisanimportant regulator of smooth muscle tone. The Thr164Ile polymorphism (rs1800888) in theADRB2 gene is rare but has profound functional consequences on receptor function and could cause lifelong elevated smooth muscle tone. We tested the hypothesis that Thr164Ile is associated with increased blood pressure, increasedfrequency ofhypertensionandincreasedrisk of cardiovascular disease (CVD). Subjects. A total of 66 750 individuals from two large Danish general population studies were genotyped, and 1943 Thr164Ile heterozygotes and 16 homozygoteswere identified. Results. Thr164Ile genotype was associated with increased systolic and diastolic blood pressure in women (trend: P = 0.04 and 0.02): systolic and diastolic blood pressure increased by 5% and 2%, respectively, in female homozygotes compared with female noncarriers. All female Thr164Ile homozygotes had hypertension compared with 58% of female heterozygotes and 54% of female noncarriers (chisquare: P = 0.001). Female Thr164Ile homozygotes and heterozygotes had odds ratios for ischaemic heart disease (IHD) of 2.93 (0.56-15.5) and 1.28 (1.03-1.61), respectively, comparedwith female noncarriers (trend: P = 0.007). These differences were not observed in men. Furthermore, Gly16Arg (rs1042713) and Gln27Glu (rs1042714) in the ADRB2gene were not associated with blood pressure, hypertension or CVD either in the population overall or inwomenandmenseparately. Conclusions. ADRB2 Thr164Ile is associated with increased blood pressure, increased frequency of hypertension and increased risk of IHD amongst womeninthegeneralpopulation. Thesefindings, particularly forhomozygotes, arenovel.