Gender-specific association between Apelin/APJ gene polymorphisms and hypertension risk in Southeast China

Wu, Xiaodan; Zhang, Na; Liang, Min; Li, Weilin; Lin, Bin; Xiao, Yi-rong; Li, Yanzhen; Zeng, Kai; Lin, Chi-Chung

doi:10.1016/j.gene.2018.05.079

Cited by 8 publications

(6 citation statements)

References 29 publications

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“…Sex differences are well established for other peptides involved in BP control such as angiotensin (1‐7) and ET‐1 43,44 . It is noteworthy that the apelin gene is located on the X chromosome, and there are sex‐specific genetic polymorphisms of both apelin and its receptor that confer differing risks of hypertension 45 . Relevant to our findings of sex differences in plasma apelin concentration is the fact that there is reciprocal regulation between the RAAS and apelin system.…”

Section: Discussionsupporting

confidence: 67%

“…43,44 It is noteworthy that the apelin gene is located on the X chromosome, and there are sex-specific genetic polymorphisms of both apelin and its receptor that confer differing risks of hypertension. 45 Relevant to our findings of sex differences in plasma apelin concentration is the fact that there is reciprocal regulation between the RAAS and apelin system. In a rodent model of heart failure, infusion of angiotensin II downregulated cardiac apelin expression and this was prevented by blockade of the angiotensin II type 1 receptor.…”

Section: Discussionmentioning

confidence: 58%

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Apelin is expressed throughout the human kidney, is elevated in chronic kidney disease & associates independently with decline in kidney function

Nyimanu

Chapman

Gallacher

et al. 2022

Brit J Clinical Pharma

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Aims Chronic kidney disease (CKD) is common and cardiovascular disease (CVD) is its commonest complication. The apelin system is a potential therapeutic target for CVD but data relating to apelin in CKD are limited. We examined expression of the apelin system in human kidney, and investigated apelin and Elabela/Toddler (ELA), the endogenous ligands for the apelin receptor, in patients with CKD. Methods Using autoradiography, immunohistochemistry and enzyme‐linked immunosorbent assay, we assessed expression of apelin, ELA and the apelin receptor in healthy human kidney, and measured plasma apelin and ELA in 155 subjects (128 patients with CKD, 27 matched controls) followed up for 5 years. Cardiovascular assessments included blood pressure, arterial stiffness (pulse wave velocity) and brachial artery flow‐mediated dilation. Surrogate markers of endothelial function (plasma asymmetric dimethylarginine and endothelin‐1) and inflammation (C‐reactive protein and interleukin‐6) were measured. Results The apelin system was expressed in healthy human kidney, throughout the nephron. Plasma apelin concentrations were 60% higher in women than men (6.48 [3.62–9.89] vs. 3.95 [2.02–5.85] pg/mL; P < .0001), and increased as glomerular filtration rate declined (R = −0.41, P < .0001), and albuminuria rose (R = 0.52, P < .0001). Plasma apelin and ELA were associated with vascular dysfunction. Plasma apelin associated independently with a 50% decline in glomerular filtration rate at 5 years. Conclusion We show for the first time that the apelin system is expressed in healthy human kidney. Plasma apelin is elevated in CKD and may be a potential biomarker of risk of decline in kidney function. Clinical studies exploring the therapeutic potential of apelin agonism in CKD are warranted.

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 58%

Apelin is expressed throughout the human kidney, is elevated in chronic kidney disease & associates independently with decline in kidney function

Nyimanu

Chapman

Gallacher

et al. 2022

Brit J Clinical Pharma

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“…Apelin treatment has been proven beneficial for conditions as diverse as hypertension, atherosclerosis, myocardial infarction, and other cardiovascular diseases (Zhou et al, 2016). Numerous studies have shown that APLN/APLNR polymorphisms are associated with the risk of several diseases such as hypertension, CAD, and diabetes mellitus (Nowzari et al, 2018;Wu et al, 2018;Zhang et al, 2019). Our results demonstrated that the T allele of the rs2235310 polymorphism and the C allele of the rs9943582 polymorphism were risk factors in the development of CHD.…”

Section: Discussionmentioning

confidence: 50%

Association of Apelin and Apelin Receptor Polymorphisms With the Risk of Comorbid Depression and Anxiety in Coronary Heart Disease Patients

Wang

Liu

et al. 2020

Front. Genet.

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The Apelin (APLN)/apelin receptor (APLNR) signaling pathway is a newly identified regulator in various cardiovascular diseases, which is considered as a candidate pathway for the occurrence of coronary heart disease (CHD), depression, and anxiety. The goal of this study was to investigate the association between APLN/APLNR gene polymorphisms and the risk of depression and anxiety in CHD patients. To this end, a case-control study involving 269 CHD patients and 184 healthy control individuals was conducted. The 269 patients with CHD including 122 patients with and 147 patients without depression, and 56 patients with and 213 patients without anxiety Four single nucleotide polymorphisms were selected and successfully genotyped using Sanger sequencing. The APLN rs2235310T allele and APLNR rs9943582C allele were found to be associated with an increased risk of CHD after multiple test correction (Padjust < 0.05). The patients with CHD who carried the rs9943582C allele had a higher risk of depression, after adjusting for alcohol drinking habits, insomnia, hypertension, and stroke history, with the Bonferroni correction (P-adjust = 0.018). The APLNR rs2282623 T allele was associated with an increased risk of anxiety in CHD patients after adjusting for related disease complications, with the Bonferroni correction (Padjust = 0.022). We reported for the first time that the APLN rs2235310 and APLNR rs2282623 polymorphisms are associated with the risks of psychiatric disorders in CHD patients and may serve as novel biomarkers for therapy.

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“…14,19,25,29–33 Two studies only included other apelin polymorphisms were excluded. 18,19 Six studies were excluded, from which appropriate data cannot be extracted. 4,10,11,15,34,35 Among excluded studies, although two studies based on the Indian population and Mexican-Mestizo ethnic origin were identified, these two studies were excluded because of limited sample size and low frequency of mutated alleles, the OR value of which cannot be estimated.…”

Section: Resultsmentioning

confidence: 99%

“…These single nucleotide polymorphism (SNP), loci include rs3115757, rs56204867, rs7119375, rs3761581, rs909656, rs5975126, rs10501367, rs11544374, rs2235306, and rs2235307 of apelin or APJ. 4,10–19 And the results were debatable among different regions and genders.…”

Section: Introductionmentioning

confidence: 96%

The association between apelin polymorphisms and hypertension in China: A meta-analysis

Wang

Liu

Jia

et al. 2019

J Renin Angiotensin Aldosterone Syst

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Introduction:Apelin plays an important part in regulating blood pressure, metabolism, and the development of cancer. Recent studies have investigated the association of apelin polymorphisms and hypertension risk, but no meta-analysis has been conducted.Materials and methods:Five studies were included in this meta-analysis in total. The pooled odds ratio and its corresponding 95% confidence interval were calculated by the random-effect model.Results:The overall pooled odds ratio of the distribution of rs3761581 G allelic frequency was 0.90 (95% confidence interval: 0.82–1.00). In female participants, the pooled odds ratio of the frequency of G allele was 1.01 (95% confidence interval: 0.89–1.14). For males, the pooled odds ratio of the frequency of G allele was 0.69 (95% confidence interval: 0.46–1.03). As for rs56204867, the overall pooled odds ratio of the frequency of G allele was 1.09 (95% confidence interval: 0.86–1.37). In females, the pooled odds ratio of the frequencies of the G allele was 1.05 (95% confidence interval: 0.86–1.29). In male participants, the frequency of G allele did not show significant correlation with hypertension (pooled odds ratio=1.21 95% confidence interval: 0.81–1.79).Conclusion:This meta-analysis revealed that there was no correlation between apelin polymorphisms, rs3761581 and rs56204867, and the prevalence of hypertension.

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Gender-specific association between Apelin/APJ gene polymorphisms and hypertension risk in Southeast China

Cited by 8 publications

References 29 publications

Apelin is expressed throughout the human kidney, is elevated in chronic kidney disease & associates independently with decline in kidney function

Apelin is expressed throughout the human kidney, is elevated in chronic kidney disease & associates independently with decline in kidney function

Association of Apelin and Apelin Receptor Polymorphisms With the Risk of Comorbid Depression and Anxiety in Coronary Heart Disease Patients

The association between apelin polymorphisms and hypertension in China: A meta-analysis

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