The ß(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.
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.
We genotyped 9185 individuals from the adult Danish general population.
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.
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.
Large multifunctional protease LMP2 (Arg60-->His), LMP7 (Lys145-->Gln) and PSMA6 (C(-8)-->G) gene allelic polymorphisms in 147 young patients with essential hypertension and in 208 practically healthy people were determinated. It was shown that interrelation of genotypes Arg/Arg, Arg/His and His/His in LMP2 gene polymorphisms account 42.5 %, 46.4% and 11.1% correspondingly (in control--63.9%, 28.6%, 7.5%; P = 0.001 by c2-test). Allelic variants of PSMA6 dispense the next manner: C/C--76.2%, C/G--21.1%, G/G--2.7% in adolescents with EH (in control--69.8%, 29.7% and 0.5% correspondingly, P = 0,047). Analysis of LMP7 gene polymorphism showed identical frequency of different genotypes in patients (Lys/Lys--92.4%, Lys/Gln--7.6%, Gln/Gln--0%) and practically healthy people (97.3%, 2.7%, 0% correspondingly; P = 0.16). Obtained data suggest the LMP2 and PSMA6 gene polymorphisms significance as the risk factors of essential hypertension in adolescents.
Preeclampsia is a complex heterogeneous disease commonly defined by new-onset hypertension and proteinuria in pregnancy. Women experiencing preeclampsia have increased risk for cardiovascular diseases (CVD) later in life. Preeclampsia and CVD share risk factors and pathophysiologic mechanisms, including dysregulated inflammation and raised blood pressure. Despite commonalities, little is known about the contribution of shared genes (pleiotropy) to these diseases. This study aimed to investigate whether genetic risk factors for hypertension or inflammation are pleiotropic by also being associated with preeclampsia.
We genotyped 122 single nucleotide polymorphisms (SNPs) in women with preeclampsia (n?=?1006) and nonpreeclamptic controls (n?=?816) from the Norwegian HUNT Study. SNPs were chosen on the basis of previously reported associations with either nongestational hypertension or inflammation in genome-wide association studies. The SNPs were tested for association with preeclampsia in a multiple logistic regression model.
The minor (G) allele of the intronic SNP rs17367504 in the gene methylenetetrahydrofolate reductase (MTHFR) was associated with a protective effect on preeclampsia (odds ratio 0.65, 95% confidence interval 0.53-0.80) in the Norwegian cohort. This association did not replicate in an Australian preeclampsia case-control cohort (P?=?0.68, odds ratio 1.05, 95% confidence interval 0.83-1.32, minor allele frequency?=?0.15).
MTHFR is important for regulating transmethylation processes and is involved in regulation of folate metabolism. The G allele of rs17367504 has previously been shown to protect against nongestational hypertension. Our study suggests a novel association between this allele and reduced risk for preeclampsia. This is the first study associating the minor (G) allele of a SNP within the MTHFR gene with a protective effect on preeclampsia, and in doing so identifying a possible pleiotropic protective effect on preeclampsia and hypertension.
Cites: Am J Clin Nutr. 2015 Mar;101(3):646-5825733650
Cites: PLoS One. 2014 Feb 05;9(2):e8749724505291
Cites: Bioinformatics. 2008 Dec 15;24(24):2938-918974171
OBJECTIVE: Smoking is a risk factor for increased carotid artery intima-media thickness (IMT). The apolipoprotein E (apoE) 4 allele has been associated with cardiovascular diseases, but the role of apoE in regard to intima-media thickness (IMT) has remained controversial. The objective was to investigate whether there is some gene-environment interaction between smoking and apoE polymorphism.DESIGN Cross-sectional case-control study. METHODS: IMTs of 511 hypertensive and control men were measured ultrasonographically and the apoE genotypes were determined. Genotypes with the 4 allele were pooled into one group and the genotypes without it into another. RESULTS: A significant interaction between the 4 allele and smoking affecting IMT was observed among the hypertensive smokers, as assessed by analysis of covariance. The mean carotid IMT was significantly greater (1.01 versus 0.90 mm, P = 0.003) in the 4 carriers than in the subjects without 4 among the hypertensive smokers. The number of plaques was also significantly higher. No differences were found in the other subjects (hypertensive non-smokers or controls). Linear regression analysis indicated that the 4 allele was an independent determinant of IMT in the hypertensive smokers but not in the other subjects. The estimated average effect of the 4 allele on the mean IMT in the hypertensive smokers was 0.088 mm (P
Ghrelin is a gut-brain hormone, which stimulates food intake and controls energy balance. Recently, it has been shown that ghrelin may also play a role in the regulation of blood pressure (BP) by acting at the sympathetic nervous system. In the present study we genotyped six variants of the ghrelin gene and its promoter, and tested whether these single nucleotide polymorphisms (SNPs) were associated with BP levels in participants of the Finnish Diabetes Prevention Study.
The Finnish Diabetes Prevention Study was a longitudinal study where 522 subjects with impaired glucose tolerance were randomized into either an intervention or control group. DNA was available from 507 subjects (mean body mass index [BMI] 31.2+/-4.5 kg/m2, age 55+/-7 years). All six SNPs were screened by the restriction fragment length polymorphism method.
Subjects with the most common genotype combination of the following four SNPs, -604G/A, -501A/C, Leu72Met, and Gln90Leu, had the lowest systolic (131+/-11 v 137+/-13 mm Hg, P=.003) and diastolic BP levels (79+/-7 v 83+/-7 mm Hg, P=.004) at the baseline of the study and during 3 years of follow-up compared to all other genotypes. Adjustments for age, gender, antihypertensive medication, BMI, waist circumference, and alcohol intake did not change this association.
Several ghrelin gene variations were associated with BP levels in subjects with impaired glucose tolerance.
We examined the association of three known genome-wide association study loci for blood lipids that have lead traits for triglycerides with hypertension in the Tampere adult population cardiovascular risk study.
A Finnish cohort of 190 men with diagnosed hypertension and 279 controls were analyzed. Samples were genotyped for low-density lipoprotein receptor-related protein 1 rs11613352 (C>T), angiopoietin-like 3 rs2131925 (T>G), and fatty acid desaturase 1 rs174546 (C>T) polymorphisms using competitive allele-specific polymerase chain reaction technique.
At the age of 50, subjects with low-density lipoprotein receptor-related protein 1 rs11613352 (C>T) minor genotype TT had significantly more hypertension than those with the C allele (OR 5.17, CI 2.03-12.74, p G) T allele had more hypertension than those with the minor genotype GG (OR 5.02, CI 1.40-17.98, p = 0.013). Fatty acid desaturase 1 rs174546 (C>T) did not associate with hypertension.
Association of low-density lipoprotein receptor-related protein 1 rs11613352 and angiopoietin-like 3 rs2131925 with hypertension might imply a direct effect at the artery wall.
Allele and genotype distributions of the T3111C polymorphism in 3'-untranslated region of the CLOCKgene were examined in the groups of Russian patients with essential arterial hypertension (EAH) and coronary artery disease (CAD), and in control group of Russia residents of the Republic of Karelia. The genotype frequency distributions of the polymorphism examined in the EAH and CAD patients were statistically significantly different from that in the individuals without clinical signs of these diseases. The CC genotype frequency in EAH and CAD males was higher, and in the corresponding females it was lower than in males and females from the control group. Male CC carriers were characterized by a possible increased risk of EAH: OR (95% CI) = 1.42 (0.56; 3.58). Moreover, the presence of the CC genotype in males could increase the risk of CAD: OR (95% CI) = 1.58 (0.63; 3.93).
Genetic mechanisms contribute to blood pressure regulation. This study investigated whether glutathione peroxidase (GPx-3) tag single nucleotide polymorphisms (SNPs) are associated with hypertension in the rural areas of Fuxin county, Liaoning province, China.
Indigenous Fuxin Han people participated, 523 unrelated hypertensives and 547 controls were recruited. All tag SNPs of GPx-3 gene were selected. We estimated SNP allele frequency in DNA pools with pyrosequencing.
Before Bonferroni correction, C allele frequency for rs8177417 was significantly higher in hypertensives than those in controls (23.4% vs. 19.3%, P = 0.014); T allele frequency for rs3828599 was significantly lower in hypertensives than those in controls (35.6% vs. 40.8%, P = 0.009). However, when a Bonferroni correction for multiple testing was applied, only the polymorphisms rs3828599 of GPx-3 gene was associated with hypertension (P = 0.045, OR: 0.833, 95%CI: 0.695 - 0.998).
The polymorphism of rs3828599 of GPx-3 gene might be associated with hypertension in rural Han Chinese from Fuxin, Liaoning.
To investigate whether the functionally relevant -844G>A promotor polymorphism in the catalase (CAT) gene is associated with the development of essential hypertension (EH).
The investigation enrolled 2,339 unrelated ethnic Russian people, including 1,269 EH patients and 770 apparently healthy individuals. Genotyping of CAT -844G>A (rs769214) polymorphism was performed using a TaqMan real-time polymerase chain reaction assay.
The -844A allele (odds ratio (OR)=1.31; 95% confidence interval (CI), 1.04 to 1.64; ?=0.02) and the -844AA genotype (OR=1.41; 95% CI, 1.02 to 1.94; ?=0.03) were found to be related to a higher risk of EH in the smokers. No association was found between this polymorphism and EH risk in the non-smokers.
Smoking is a predisposing factor for development of EH in CAT -844AA genotype carriers.