ß2 -adrenergic receptor Thr164IIe polymorphism, blood pressure and ischaemic heart disease in 66¿750 individuals

M Thomsen; Morten Dahl; A Tybjaerg-Hansen; B G Nordestgaard

doi:10.1111/j.1365-2796.2011.02447.x

ß2 -adrenergic receptor Thr164IIe polymorphism, blood pressure and ischaemic heart disease in 66¿750 individuals

M Thomsen, Morten Dahl, A Tybjaerg-Hansen, B G Nordestgaard

13 Citationer (Scopus)

Abstract

Objectives. 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). Subjects. A total of 66750 individuals from two large Danish general population studies were genotyped, and 1943 Thr164Ile heterozygotes and 16 homozygotes were 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 (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. Conclusions. 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.

Originalsprog	Engelsk
Tidsskrift	Journal of Internal Medicine
Vol/bind	271
Udgave nummer	3
Sider (fra-til)	305-14
Antal sider	10
ISSN	0954-6820
DOI	https://doi.org/10.1111/j.1365-2796.2011.02447.x
Status	Udgivet - mar. 2012

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title = "{\ss}2 -adrenergic receptor Thr164IIe polymorphism, blood pressure and ischaemic heart disease in 66¿750 individuals",

abstract = "Objectives. 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). Subjects. A total of 66750 individuals from two large Danish general population studies were genotyped, and 1943 Thr164Ile heterozygotes and 16 homozygotes were 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 (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. Conclusions. 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.",

keywords = "Aged, Blood Pressure, Cross-Sectional Studies, Denmark, Female, Genetic Predisposition to Disease, Genotype, Humans, Hypertension, Male, Middle Aged, Muscle, Skeletal, Myocardial Ischemia, Myocytes, Smooth Muscle, Polymorphism, Single Nucleotide, Prospective Studies, Questionnaires, Receptors, Adrenergic, beta-2, Sex Factors",

author = "M Thomsen and Morten Dahl and A Tybjaerg-Hansen and Nordestgaard, {B G}",

note = "{\textcopyright} 2011 The Association for the Publication of the Journal of Internal Medicine.",

year = "2012",

month = mar,

doi = "10.1111/j.1365-2796.2011.02447.x",

language = "English",

volume = "271",

pages = "305--14",

journal = "Acta Medica Scandinavica",

issn = "0955-7873",

publisher = "Wiley-Blackwell",

number = "3",

}

TY - JOUR

T1 - ß2 -adrenergic receptor Thr164IIe polymorphism, blood pressure and ischaemic heart disease in 66¿750 individuals

AU - Thomsen, M

AU - Dahl, Morten

AU - Tybjaerg-Hansen, A

AU - Nordestgaard, B G

PY - 2012/3

Y1 - 2012/3

N2 - Objectives. 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). Subjects. A total of 66750 individuals from two large Danish general population studies were genotyped, and 1943 Thr164Ile heterozygotes and 16 homozygotes were 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 (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. Conclusions. 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.

AB - Objectives. 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). Subjects. A total of 66750 individuals from two large Danish general population studies were genotyped, and 1943 Thr164Ile heterozygotes and 16 homozygotes were 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 (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. Conclusions. 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.

KW - Aged

KW - Blood Pressure

KW - Cross-Sectional Studies

KW - Denmark

KW - Female

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Humans

KW - Hypertension

KW - Male

KW - Middle Aged

KW - Muscle, Skeletal

KW - Myocardial Ischemia

KW - Myocytes, Smooth Muscle

KW - Polymorphism, Single Nucleotide

KW - Prospective Studies

KW - Questionnaires

KW - Receptors, Adrenergic, beta-2

KW - Sex Factors

U2 - 10.1111/j.1365-2796.2011.02447.x

DO - 10.1111/j.1365-2796.2011.02447.x

M3 - Journal article

C2 - 21883537

SN - 0955-7873

VL - 271

SP - 305

EP - 314

JO - Acta Medica Scandinavica

JF - Acta Medica Scandinavica

IS - 3

ER -

ß2 -adrenergic receptor Thr164IIe polymorphism, blood pressure and ischaemic heart disease in 66¿750 individuals

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