β1-adrenoceptor gene Arg389Gly polymorphism and essential hypertension risk in general population: a meta-analysis

Abstract

The β1-adrenoceptor (ADRB1) gene Arg389Gly polymorphism has been extensively studied as a candidate gene in essential hypertension (EH), but no consensus has been reached on the relationship between this polymorphism and EH risk. To systematically explore their possible association, a meta-analysis was conducted. All relevant case-control trials in English-language publications before 1 June 2012 were identified by searching the PubMed and Embase databases. Finally, eight articles met our inclusion criteria, including a total of 5,088 patients with EH and 6,515 controls. No evidence of publication bias was found. Fixed-effects model and random-effects model were applied for dichotomous outcomes to combine results from individual studies. Overall, the Gly allelic frequency of Arg389Gly polymorphism was significantly lower in EH subjects than that in controls (Gly versus Arg: P = 0.04, OR = 0.89, 95 % CI [0.80-1.00], P heterogeneity = 0.03, I (2) = 52 %, random-effects model; GlyGly + ArgGly versus ArgArg: P = 0.02, OR = 0.86, 95 % CI [0.76-0.97], P heterogeneity = 0.08 and I (2) = 42 %, random-effect model). Subgroup analysis by ethnicity detected this association only in East Asians. In sensitivity analysis, the study by Bengtsson K was recognized as the main cause of heterogeneity, which was the only one study with the diagnostic standard for EH as systolic blood pressure (SBP) ≥ 160 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg. We concluded that the Gly allele of ADRB1 Arg389Gly polymorphism might confer lower risk for EH, especially in East Asians.

RNA N6-methyladenosine: a promising molecular target in metabolic diseases

“…Suppressing adipogenesis by promoting cell cycle transition in mitotic clonal expansion [89] YTHDF2 Inhibiting autophagy and adipogenesis by decreasing protein expression of ATG5 and ATG7 and shortening the lifespan of their m 6 A-modified mRNAs [87] Suppressing adipogenesis by increasing m 6 A methylation of CCNA2 and CDK2 and reversing the methylation effect of FTO on CCNA2 and CDK2 [90,91] Inhibiting adipogenesis via the downregulation of CCND1 [92] NAFLD FTO Down-regulating mitochondrial content and up-regulating TG deposition [101] Promoting hepatic fat accumulation by increasing the expression of lipogenic genes, including FASN, SCD and MOGAT1, and intracellular TG level in HepG2 cells [101] Increasing oxidative stress and lipid deposition [99] YTHDF2 Increasing lipid accumulation by decreasing both PPARα mRNA lifetime and expression [105] METTL3 Increasing lipid accumulation by decreasing both PPARα mRNA lifetime and expression [105] Hypertension m 6 A-SNPs EncodIing β1-adrenoreceptor, a hypertension-susceptibility candidate gene [108,109] Altering BP-related gene expression, mRNA stability and homeostasis [110] Cardiovascular diseases FTO Decreasing fibrosis and enhancing angiogenesis in mouse models of myocardial infarction [111] METTL3 Driving cardiomyocyte hypertrophy by catalyzing methylation of m 6 A on certain subsets of mRNAs [112] Decreasing eccentric cardiomyocyte remodeling and dysfunction [112] Inhibiting cellular autophagic flux and promoting apoptosis in hypoxia/reoxygenation-treated cardiomyocytes [113] Osteoporosis METTL3 Inhibiting adipogenesis and adipogenic differentiation via JAK1/STAT5/C/EBPβ pathway in bone marrow stem cells [119] Inhibiting osteoporosis pathological phenotypes, consisting of decreased bone mass and increased marrow adiposity via PTH/PTH1R signaling axis [118] FTO Promoting the differentiation of adipocyte and osteoblast by upregulating GDF11-FTO-PPARγ signalling way [116] Enhancing the stability of mRNA of proteins which function to protect osteoblasts from genotoxic damage through Hspa1a-NF-κB signaling way [120] Immune-related MDs ALKBH5 Expressing highly in organs enriched in immune cells with frequent immune reactions [10,123] METTL3 Stimulating T cell activation and the development of T lymphocytes in the thymus by regulating the translation of CD40, CD80 and TLR4 signaling adaptor TIRAP transcripts in den...…”

“…For example, the m 6 A-SNP (Lys67Arg, rs197922) in golgi SNAP receptor complex member 2 gene is positively associated with hypertension in white individuals [107]. In addition, the m 6 A-SNPs (Arg389Gly, rs1801253; Ser49Gly, rs1801253) can develop hypertension as they can encode β1-adrenoreceptor, a hypertension-susceptibility candidate gene [108,109]. rs9847953 and rs197922 have regulatory potentials to alter BP related gene expression, mRNA stability and homeostasis [110].…”

Genetics, Ancestry, and Hypertension: Implications for Targeted Antihypertensive Therapies

“…ADRB1 encodes the β-1 adrenergic receptor, a guanine nucleotide-binding regulatory protein-coupled receptor target of β-adrenergic receptor blockers. SNPs nearby or within the gene have been associated with mean arterial pressure in GWAS [21] and a lower risk of essential hypertension [41]. Vasoactive peptides including natriuretic peptides and endothelin have a well-known role in BP control.…”

Admixture mapping and fine-mapping of birth weight loci in the Black Women’s Health Study

“…In particular, the minor Gly-allele (G-allele in the DNA sequence) has been associated with low systolic and diastolic blood pressure as well as low risk of hypertension (Johnson et al 2011; Wang et al 2013). Epidemiological associations between birth weight and blood pressure make up some of the strongest evidence supporting the fetal origins of adult disease.…”