Association of gene polymorphisms in RANKL/RANK/OPG system with hypertension and blood pressure in Chinese women

Duan, Peng; Zm, Wang; Liu, Jing; Ln, Wang; Liu, Yang; Tu, Ping

doi:10.1038/jhh.2015.13

Cited by 8 publications

(6 citation statements)

References 35 publications

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“…To our knowledge, this is the first time that a statistically significant association has been found between SNPs in the RANK gene and blood pressure. Several mainly intronic SNPs of the RANK/RANKL/OPG system were associated with blood pressure in Chinese women in a previous study, [21] in which correlations with SBP and DBP were detected in SNPs of the RANK , but not the RANKL and OPG genes. However, these had low nominal statistical significance ( P < .05), so did not pass the Bonferroni correction.…”

Section: Discussionmentioning

confidence: 80%

“… [13] Since then, substantial evidence has accumulated regarding the role of these molecules in the vascular system. [ 14 15 ] The RANK/RANKL/OPG system in general, and particularly OPG, has been associated with several phenotypes related to the vascular system, such as metabolic syndrome and cardiovascular risk in osteoporotic patients, [16] serum cholesterol levels, [17] atherosclerosis, [18] vascular calcification, [19] angiogenesis, [20] hypertension, [21] and heart failure. [22] …”

Section: Introductionmentioning

confidence: 99%

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Association of a single nucleotide polymorphism of RANK gene with blood pressure in Spanish women

et al. 2020

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In addition to governing key functions in bone metabolism and the immune system, the RANK/RANKL/OPG system plays a role in the vascular system, particularly in vascular calcification and atherosclerosis. Given that these 2 phenotypes are considered a major cause of high blood pressure (BP), in this study we analyzed the association of SNPs in RANK and OPG genes with blood pressure. An observational study was conducted of 2 SNPs in the RANK gene (rs884205 and rs78326403) and 1 in the OPG gene (rs4876869) with systolic (SBP) and diastolic blood pressure (DBP) in a cohort of 695 women. Data analysis revealed a statistically significant association between the SNP rs884205 and BP pressure (SBP and DBP). Analyzing this relationship by the dominant inheritance model for this SNP (allele risk: A), women of the AA/AC genotype showed higher BP than women of the CC genotype, both for SBP ( P = .001) and for DBP ( P = .003), and these associations both surpassed the Bonferroni threshold for multiple comparisons. Multivariate regression analysis including known predictors of BP as independent variables was performed to evaluate the strength of this association, which in the case of the SNP rs884205 of the RANK gene remained statistically significant after adjustment for both SBP ( P = .0006) and DBP ( P = .005), demonstrating the key role of this SNP in BP. We report a robust association between the SNP rs884205 in RANK gene and BP in women, and this SNP is validated as a candidate in cardiovascular risk studies.

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Section: Discussionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Association of a single nucleotide polymorphism of RANK gene with blood pressure in Spanish women

et al. 2020

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“…Soysal-Atile N et al (2015) [49] reported that the A163G polymorphism of the OPG gene was not associated with microvascular or macrovascular complications of T2DM. Contrary, Duan P et al (2015) [50] presented data regarding the associations of 21 single-nucleotide polymorphisms in OPG gene with elevated diastolic blood pressure. Yet, T245G, T950C, and G1181C gene polymorphisms of the OPG gene were related to the development of peripheral arterial occlusive disease and critical limb ischemia in T2DM individuals [51].…”

Section: The Role Of Opg Gene Polymorphisms In Diabetes-related Vascumentioning

confidence: 99%

Single sample and serial measurements of osteoprotegerin level as a target of therapy in type 2 diabetes mellitus?

Berezin¹

2016

bmgt

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Osteoprotegerin (OPG) is a soluble member of the tumor necrosis factor receptor superfamily, which exhibits the close link to cardiovascular (CV) disease in type 2 diabetes mellitus (T2DM). Recent clinical studies have been shown that elevated OPG might be a marker of vascular calcification / remodeling and CV events and CV mortality in T2DM without known CV disease. However, it remains unclear whether OPG would be a target for therapy of diabetics with antidiabetic drugs and statins. The aim of the mini review: to summarize knowledge with respect to OPG utilization as predictor of CV adverse effects and as a target of therapy in T2DM. The review is discussed the evidence regarding possibility to prevent microvascular and macrovascular complications in diabetics through control of OPG level as a target in therapy. Although there are not irresistible findings that the post-treatment OPG level in diabetics and CV events might be related, possibility to use OPG for risk stratification of vascular remodeling / ectopic calcification and CV-related mortality in T2DM appears to be attractive. The future investigations are needed to explain whether serum OPG would be informative for biomarker-guided therapy in T2DM individuals.

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“…This inflammatory pathway has been implicated in hypertension-induced renal dysfunction in murine models (51) and with endothelial dysfunction in overweight/obese and older humans (52). There was suggested evidence of association of variants in TNFRSF11A with BP traits in Chinese women (53).…”

Section: Biological Relevance Of Newly Identified Bp Locimentioning

confidence: 99%

A multi-ancestry genome-wide study incorporating gene–smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure

Sung

Fuentes

Winkler

et al. 2019

Human Molecular Genetics

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Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.

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Association of gene polymorphisms in RANKL/RANK/OPG system with hypertension and blood pressure in Chinese women

Cited by 8 publications

References 35 publications

Association of a single nucleotide polymorphism of RANK gene with blood pressure in Spanish women

Association of a single nucleotide polymorphism of RANK gene with blood pressure in Spanish women

Single sample and serial measurements of osteoprotegerin level as a target of therapy in type 2 diabetes mellitus?

A multi-ancestry genome-wide study incorporating gene–smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure

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