Gender-Specific Association of<i>ATP2B1</i>Variants with Susceptibility to Essential Hypertension in the Han Chinese Population

Xu, Jin; Qian, Hai-xia; Hu, Supei; Liu, Liya; Zhou, Mi; Feng, Mei; Su, Jia; Ji, Li

doi:10.1155/2016/1910565

Cited by 8 publications

(3 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In another study conducted by Kayima et al [ 33 ] on a Ugandan population, it was reported that rs2681492 was significantly associated with HTN in hypertensive individuals. Likewise, SNPs on ATP2B1 (rs17249754, rs2681472, and rs2681492) were reported to be in linkage disequilibrium and located in the same linkage disequilibrium block in the Chinese population [ 84 ].…”

Section: Discussionmentioning

confidence: 99%

Hypertension in African Populations: Review and Computational Insights

Mabhida

Mashatola

Kaur

et al. 2021

Genes

View full text Add to dashboard Cite

Hypertension (HTN) is a persistent public health problem affecting approximately 1.3 billion individuals globally. Treatment-resistant hypertension (TRH) is defined as high blood pressure (BP) in a hypertensive patient that remains above goal despite use of ≥3 antihypertensive agents of different classes including a diuretic. Despite a plethora of treatment options available, only 31.0% of individuals have their HTN controlled. Interindividual genetic variability to drug response might explain this disappointing outcome because of genetic polymorphisms. Additionally, the poor knowledge of pathophysiological mechanisms underlying hypertensive disease and the long-term interaction of antihypertensive drugs with blood pressure control mechanisms further aggravates the problem. Furthermore, in Africa, there is a paucity of pharmacogenomic data on the treatment of resistant hypertension. Therefore, identification of genetic signals having the potential to predict the response of a drug for a given individual in an African population has been the subject of intensive investigation. In this review, we aim to systematically extract and discuss African evidence on the genetic variation, and pharmacogenomics towards the treatment of HTN. Furthermore, in silico methods are utilized to elucidate biological processes that will aid in identifying novel drug targets for the treatment of resistant hypertension in an African population. To provide an expanded view of genetic variants associated with the development of HTN, this study was performed using publicly available databases such as PubMed, Scopus, Web of Science, African Journal Online, PharmGKB searching for relevant papers between 1984 and 2020. A total of 2784 articles were reviewed, and only 42 studies were included following the inclusion criteria. Twenty studies reported associations with HTN and genes such as AGT (rs699), ACE (rs1799752), NOS3 (rs1799983), MTHFR (rs1801133), AGTR1 (rs5186), while twenty-two studies did not show any association within the African population. Thereafter, an in silico predictive approach was utilized to identify several genes including CLCNKB, CYPB11B2, SH2B2, STK9, and TBX5 which may act as potential drug targets because they are involved in pathways known to influence blood pressure. Next, co-expressed genes were identified as they are controlled by the same transcriptional regulatory program and may potentially be more effective as multiple drug targets in the treatment regimens for HTN. Genes belonging to the co-expressed gene cluster, ACE, AGT, AGTR1, AGTR2, and NOS3 as well as CSK and ADRG1 showed enrichment of G-protein-coupled receptor activity, the classical targets of drug discovery, which mediate cellular signaling processes. The latter is of importance, as the targeting of co-regulatory gene clusters will allow for the development of more effective HTN drug targets that could decrease the prevalence of both controlled and TRH.

show abstract

Section: Discussionmentioning

confidence: 99%

Hypertension in African Populations: Review and Computational Insights

Mabhida

Mashatola

Kaur

et al. 2021

Genes

View full text Add to dashboard Cite

show abstract

“…In our study, rs11105378 was in linkage disequilibrium with rs2681472 and rs1401982. A previous study involving Chinese participants found that rs1105378 was significantly associated with hypertension 44 . Alleles such as SNPs rs2681492, rs2681472, and rs17249754, which are in strong linkage disequilibrium with rs1105378, have been suggested as genetic markers for the development of hypertension.…”

Section: Discussionmentioning

confidence: 99%

ATP2B1 gene polymorphisms associated with resistant hypertension in the Japanese population

Kobayashi,

Yatsu,

Haruna

et al. 2024

J of Clinical Hypertension

View full text Add to dashboard Cite

Single‐nucleotide polymorphisms (SNP) of ATP2B1 gene are associated with essential hypertension but their association with resistant hypertension (RHT) remains unexplored. The authors examined the relationship between ATP2B1 SNPs and RHT by genotyping 12 SNPs in ATP2B1 gene of 1124 Japanese individuals with lifestyle‐related diseases. Patients with RHT had inadequate blood pressure (BP) control using three antihypertensive drugs or used ≥4 antihypertensive drugs. Patients with controlled hypertension had BP controlled using ≤3 antihypertensive drugs. The association between each SNP and RHT was analyzed by logistic regression. The final cohort had 888 (79.0%) and 43 (3.8%) patients with controlled hypertension and RHT, respectively. Compared with patients homozygous for the minor allele of each SNP in ATP2B1, a significantly higher number of patients carrying the major allele at 10 SNPs exhibited RHT (most significant at rs1401982: 5.8% vs. 0.8%, p = .014; least significant at rs11105378: 5.7% vs. 0.9%, p = .035; most nonsignificant at rs12817819: 5.1% vs. 10%, p = .413). After multivariate adjustment for age, sex, systolic BP, and other confounders, the association remained significant for rs2681472 and rs1401982 (OR: 7.60, p < .05 and OR: 7.62, p = .049, respectively). Additionally, rs2681472 and rs1401982 were in linkage disequilibrium with rs11105378. This study identified two ATP2B1 SNPs associated with RHT in the Japanese population. rs1401982 was most closely associated with RHT, and major allele carriers of rs1401982 required significantly more antihypertensive medications. Analysis of ATP2B1 SNPs in patients with hypertension can help in early prediction of RHT and identification of high‐risk patients who are more likely to require more antihypertensive medications.

show abstract

“…In contrast to GWAS data for ATP2B4, SNPs located in ATP2B1, the gene encoding PMCA1, have been strongly associated with CVDs, including hypertension, coronary artery disease and MI (Tabara et al, 2010;Takeuchi et al, 2010;Wang Y. et al, 2013;Xu et al, 2016;Jamshidi et al, 2018;Sombie et al, 2019). The association of ATP2B1 with hypertension has been shown in numerous studies across different ethnic groups; to date, there are at least six different SNPs within ATP2B1 which are associated with elevated blood pressure (Tabara et al, 2010;Takeuchi et al, 2010;Wang Y. et al, 2013;Xu et al, 2016;Jamshidi et al, 2018;Sombie et al, 2019).…”

Section: Pmcasmentioning

confidence: 91%

Targeting Ca2 + Handling Proteins for the Treatment of Heart Failure and Arrhythmias

2020

View full text Add to dashboard Cite

Diseases of the heart, such as heart failure and cardiac arrhythmias, are a growing socioeconomic burden. Calcium (Ca 2+) dysregulation is key hallmark of the failing myocardium and has long been touted as a potential therapeutic target in the treatment of a variety of cardiovascular diseases (CVD). In the heart, Ca 2+ is essential for maintaining normal cardiac function through the generation of the cardiac action potential and its involvement in excitation contraction coupling. As such, the proteins which regulate Ca 2+ cycling and signaling play a vital role in maintaining Ca 2+ homeostasis. Changes to the expression levels and function of Ca 2+-channels, pumps and associated intracellular handling proteins contribute to altered Ca 2+ homeostasis in CVD. The remodeling of Ca 2+-handling proteins therefore results in impaired Ca 2+ cycling, Ca 2+ leak from the sarcoplasmic reticulum and reduced Ca 2+ clearance, all of which contributes to increased intracellular Ca 2+. Currently, approved treatments for targeting Ca 2+ handling dysfunction in CVD are focused on Ca 2+ channel blockers. However, whilst Ca 2+ channel blockers have been successful in the treatment of some arrhythmic disorders, they are not universally prescribed to heart failure patients owing to their ability to depress cardiac function. Despite the progress in CVD treatments, there remains a clear need for novel therapeutic approaches which are able to reverse pathophysiology associated with heart failure and arrhythmias. Given that heart failure and cardiac arrhythmias are closely associated with altered Ca 2+ homeostasis, this review will address the molecular changes to proteins associated with both Ca 2+handling and-signaling; their potential as novel therapeutic targets will be discussed in the context of pre-clinical and, where available, clinical data.

show abstract

Gender-Specific Association ofATP2B1Variants with Susceptibility to Essential Hypertension in the Han Chinese Population

Cited by 8 publications

References 37 publications

Hypertension in African Populations: Review and Computational Insights

Hypertension in African Populations: Review and Computational Insights

ATP2B1 gene polymorphisms associated with resistant hypertension in the Japanese population

Targeting Ca2 + Handling Proteins for the Treatment of Heart Failure and Arrhythmias

Contact Info

Product

Resources

About