Exploring the Genetic Associations Between the Use of Statins and Alzheimer's Disease

Lee, Jibeom; Park, Suhyeon; Kim, Yumin; Kim, Hyun Min; Oh, Chang‐Myung

doi:10.12997/jla.2022.11.2.133

Cited by 4 publications

(3 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results indicated that four genes including the ABCG1 gene were associated with both diseases 124 . Genomic data from AD shows that ABCG1 expression is upregulated while taking statins reduced ABCG1 expression in the blood of AD patients 125 . Table 1 summarizes ABCG1's effects on AD.…”

Section: Abcg1 In Admentioning

confidence: 99%

See 1 more Smart Citation

The role of ATP‐binding cassette transporter G1 (ABCG1) in Alzheimer's disease: A review of the mechanisms

Yazdi,

Alavi,

Roohbakhsh

2024

Basic Clin Pharma Tox

View full text Add to dashboard Cite

The maintenance of cholesterol homeostasis is essential for central nervous system function. Consequently, factors that affect cholesterol homeostasis are linked to neurological disorders and pathologies. Among them, ATP‐binding cassette transporter G1 (ABCG1) plays a significant role in atherosclerosis. However, its role in Alzheimer's disease (AD) is unclear. There is inconsistent information regarding ABCG1's role in AD. It can increase or decrease amyloid β (Aβ) levels in animals' brains. Clinical studies show that ABCG1 is involved in AD patients' impairment of cholesterol efflux capacity (CEC) in the cerebrospinal fluid (CSF). Lower Aβ levels in the CSF are correlated with ABCG1‐mediated CEC dysfunction. ABCG1 modulates α‐, β‐, and γ‐secretase activities in the plasma membrane and may affect Aβ production in the mitochondria‐associated endoplasmic reticulum (ER) membrane (MAM) cell compartment. Despite contradictory findings regarding ABCG1's role in AD, this review shows that ABCG1 has a role in Aβ generation via modulation of membrane secretases. It is, however, necessary to investigate the underlying mechanism(s). ABCG1 may also contribute to AD pathology through its role in apoptosis and oxidative stress. As a result, ABCG1 plays a role in AD and is a candidate for drug development.

show abstract

Section: Abcg1 In Admentioning

confidence: 99%

“…124 Genomic data from AD shows that ABCG1 expression is upregulated while taking statins reduced ABCG1 expression in the blood of AD patients. 125 Table 1 summarizes ABCG1's effects on AD. In humans, the ABCG1 gene resides on chromosome 21 suggesting that it may have a role(s) in Down syndrome (DS) pathology.…”

Section: Abcg1 In Admentioning

confidence: 99%

The role of ATP‐binding cassette transporter G1 (ABCG1) in Alzheimer's disease: A review of the mechanisms

Yazdi,

Alavi,

Roohbakhsh

2024

Basic Clin Pharma Tox

View full text Add to dashboard Cite

show abstract

“…Therefore, the prediction of drug-related adverse events in a specific patient, appropriate drug selection, and avoidance of adverse events are expected to improve drug adherence and clinical outcomes. With recent advances in genetic research [8], several genome-wide association studies (GWASs) have reported genetic loci associated with ACEI-related cough. Candidate genes include NTSR1 [9], NELL1 [10], and CLASP1 [11].…”

mentioning

confidence: 99%

A randomized trial of genotype-guided perindopril use

Lee,

Kang

et al. 2023

Journal of Hypertension

View full text Add to dashboard Cite

Objective: Cough caused by angiotensin-converting enzyme inhibitors (ACEIs) limits their clinical application and cardiovascular benefits. This randomized trial investigated whether genotype-guided perindopril use could reduce drug-related cough in 20 to 79-year-old individuals with hypertension. Methods: After screening 120 patients and randomization, 68 were assigned to genotyping (n = 41) and control (n = 27) groups. NELL1 p.Arg382Trp (rs8176786) and intron (rs10766756) genotype information was used to subdivide the genotyping group into high-risk and low-risk subgroups with at least one or no risk alleles for ACEI-related cough, respectively. The high-risk subgroup received candesartan (8 mg/day) for 6 weeks, whereas the low-risk subgroup received perindopril (4 mg/day). The control group, which was not genotyped, received perindopril (4 mg/day). The primary outcome variables were cough and moderate/severe cough; the secondary outcome variable was any adverse event. Results: During the 6-week period, the risk of cough was lower in the genotyping group than in the control group [five (12.2%) and nine (33.3%) participants, respectively; hazard ratio: 0.25; log-rank P = 0.017]. The moderate/severe cough risk was also lower in the genotyping group [one (2.4%) and five (18.5%) participants, respectively; hazard ratio: 0.12; log-rank P = 0.025]. Differences in cough (hazard ratio: 0.56; log-rank P = 0.32) and moderate/severe cough risk (hazard ratio: 0.26; log-rank P = 0.19) between the low-risk and control groups were not significant. The risk of total adverse events was similar between any two groups. Conclusion: Cough risk was lower during genotype-guided treatment than during conventional treatment. These results support the utility of NELL1 variant data in clinical decision making to personalize renin-angiotensin system blocker therapy use. Trial Registration: ClinicalTrials.gov number: NCT05535595 (retrospectively registered at September 7, 2022). Video Abstract style, http://links.lww.com/HJH/C257

show abstract

Are Only p-Values Less Than 0.05 Significant? A p-Value Greater Than 0.05 Is Also Significant!

Kwak

2023

J Lipid Atheroscler

View full text Add to dashboard Cite

Statistical hypothesis testing compares the significance probability value and the significance level value to determine whether or not to reject the null hypothesis. This concludes “significant or not significant.” However, since this process is a process of statistical hypothesis testing, the conclusion of “statistically significant or not statistically significant” is more appropriate than the conclusion of “significant or not significant.” Also, in many studies, the significance level is set to 0.05 to compare with the significance probability value, p -value. If the p -value is less than 0.05, it is judged as “significant,” and if the p -value is greater than 0.05, it is judged as “not significant.” However, since the significance probability is a value set by the researcher according to the circumstances of each study, it does not necessarily have to be 0.05. In a statistical hypothesis test, the conclusion depends on the setting of the significance level value, so the researcher must carefully set the significance level value. In this study, the stages of statistical hypothesis testing were examined in detail, and the exact conclusions accordingly and the contents that should be considered carefully when interpreting them were mentioned with emphasis on statistical hypothesis testing and significance level. In 11 original articles published in the Journal of Lipid and Atherosclerosis in 2022, the interpretation of hypothesis testing and the contents of the described conclusions were reviewed from the perspective of statistical hypothesis testing and significance level, and the content that I would like to be supplemented was mentioned.

show abstract

Exploring the Genetic Associations Between the Use of Statins and Alzheimer's Disease

Cited by 4 publications

References 77 publications

The role of ATP‐binding cassette transporter G1 (ABCG1) in Alzheimer's disease: A review of the mechanisms

The role of ATP‐binding cassette transporter G1 (ABCG1) in Alzheimer's disease: A review of the mechanisms

A randomized trial of genotype-guided perindopril use

Are Only p-Values Less Than 0.05 Significant? A p-Value Greater Than 0.05 Is Also Significant!

Contact Info

Product

Resources

About