Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
J Intern Med. 2012 Mar;271(3):305-14. doi: 10.1111/j.1365-2796.2011.02447.x. Epub 2011 Sep 29.
The β(2) -adrenergic receptor (ADRB2) is located on smooth muscle cells and is an important regulator of smooth muscle tone. The Thr164Ile polymorphism (rs1800888) in the ADRB2 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, increased frequency of hypertension and increased risk of cardiovascular disease (CVD).
A total of 66 750 individuals from two large Danish general population studies were genotyped, and 1943 Thr164Ile heterozygotes and 16 homozygotes were identified.
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 (chi-square: 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, compared with female noncarriers (trend: P = 0.007). These differences were not observed in men. Furthermore, Gly16Arg (rs1042713) and Gln27Glu (rs1042714) in the ADRB2 gene were not associated with blood pressure, hypertension or CVD either in the population overall or in women and men separately.
ADRB2 Thr164Ile is associated with increased blood pressure, increased frequency of hypertension and increased risk of IHD amongst women in the general population. These findings, particularly for homozygotes, are novel.
β(2)-肾上腺素能受体（ADRB2）位于平滑肌细胞上，是平滑肌张力的重要调节剂。ADRB2 基因中的 Thr164Ile 多态性（rs1800888）虽然罕见，但对受体功能有深远的影响，可能导致终生平滑肌张力升高。我们检验了这样的假说，即 Thr164Ile 与血压升高、高血压发病率增加以及心血管疾病（CVD）风险增加相关。
来自两项丹麦大型一般人群研究的共 66750 人进行了基因分型，确定了 1943 名 Thr164Ile 杂合子和 16 名纯合子。
Thr164Ile 基因型与女性的收缩压和舒张压升高相关（趋势：P=0.04 和 0.02）：与女性非携带者相比，女性纯合子的收缩压和舒张压分别升高 5%和 2%。所有女性 Thr164Ile 纯合子均患有高血压，而女性杂合子的发病率为 58%，女性非携带者的发病率为 54%（卡方检验：P=0.001）。与女性非携带者相比，女性 Thr164Ile 纯合子和杂合子患缺血性心脏病（IHD）的比值比分别为 2.93（0.56-15.5）和 1.28（1.03-1.61）（趋势：P=0.007）。在男性中未观察到这些差异。此外，ADRB2 基因中的 Gly16Arg（rs1042713）和 Gln27Glu（rs1042714）无论在总体人群中还是在女性和男性中，均与血压、高血压或 CVD 无关。
在一般人群中，ADRB2 Thr164Ile 与女性的血压升高、高血压发病率增加以及 IHD 风险增加相关。这些发现，尤其是对纯合子的发现，是新颖的。
