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ACE2 role in SARS-CoV-2 infectivity and Covid-19 severity

Azizan E, Brown M

Malays J Pathol, 2020 Dec;42(3):363-367.
PMID: 33361716

In 2003, it was discovered that the entry receptor for the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) is a protein called the angiotensin-converting enzyme 2 (ACE2). This protein is present in a number of cell types, including those from the respiratory tract. Soon after the emergence of SARS-CoV-2 that is responsible for the disease Covid-19, scientists found that ACE2 was also used by the new coronavirus to infect cells. This opened some interesting possibilities to explain the striking variation in risks of catching and dying from Covid-19. The best recognised of these are the much higher risk of serious illness in older than younger people, in men than women, and in those with pre-existing comorbidities such as hypertension and cardiovascular diseases. There are several ways in which the ACE2 protein might contribute to this variation. The most obvious would be if there is more ACE2, there would be more entry points for the virus to infect the cell, e.g. in older people or in men. However, the evidence for this is rather small, partly because it is not that easy to obtain representative healthy tissues. Alternatively, it could be related to ACE2 membership of a family of proteins that has one end of the protein anchored inside the cell while most of the protein protrudes from the outside of the cell which therefore can be shed when cleaved by proteases at the cell membrane. Herein we review current evidence and theories of ACE2 role on SARS-CoV-2 infectivity and Covid-19 severity.
ISH ADA-04 TRANSCRIPTOME PATHWAY ANALYSIS OF AUTONOMOUS AND PHYSIOLOGICAL ALDOSTERONE-PRODUCING HUMAN TISSUE

Zhou J, Lam B, Neogi S, Yeo G, Azizan E, Brown M

J Hypertens, 2016 Sep;34 Suppl 1 - ISH 2016 Abstract Book:e40.
PMID: 27753883

Primary aldosteronism (PA) is the most common type of secondary hypertension occurring in ∼10% of hypertensive patients. Up to 50% of PA is caused by aldosterone-producing adenomas (APA). This study is to identify the potential biological processes and canonical pathways involved with aldosterone regulation, APA formation, or APA and ZG cell functions.
Associated genetic polymorphisms and clinical manifestations in systemic lupus erythematosus in Asian populations - A systematic literature review

Abd Talib AKA, Tan SC, Jamal R, Azizan EA, Shaharir SS, Abdul Murad NA

Med J Malaysia, 2021 07;76(4):541-550.
PMID: 34305116

INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic and life-threatening autoimmune disease. Its prevalence and clinical manifestations are known to be particularly severe in the Asian populations. Although genetics is known to play an important role in SLE susceptibility and clinical manifestations, the specific polymorphisms associated with these phenotypes in Asia are unclear. Therefore, we aim to review the association of SLE genetic polymorphisms with lupus manifestations across Asian populations and their role in the pathogenesis of SLE.
METHODS: A systematic search was conducted on PubMed, EBSCOHost, and Web of Science. We identified 22 casecontrol studies that matched our inclusion and exclusion criteria. Information such as study characteristics, genetic polymorphisms associated with SLE, and organ manifestations was extracted and reported in this review.
RESULTS: In total, 30 polymorphisms in 16 genes were found to be associated with SLE among Asians. All included polymorphisms also reported associations with various SLE clinical features. The association of rs1234315 in TNFSF4 linking to SLE susceptibility (P=4.17x10-17 OR=1.45 95% CI=1.34-1.59) and musculoskeletal manifestation (P=3.35x10-9, OR=1.37, 95%CI= 1.23-1.51) might be the most potential biomarkers to differentiate SLE between Asian and other populations. In fact, these associated genetic variants were found in loci that were implicated in immune systems, signal transduction, gene expression that play important roles in SLE pathogenesis.
DISCUSSIONS AND CONCLUSIONS: This review summarized the potential correlation between 30 genetic polymorphisms associated with SLE and its clinical manifestations among Asians. More efforts in dissecting the functional implications and linkage disequilibrium of associated variants may be required to validate these findings.
Oral trehalose maybe helpful for patients with spinocerebellar ataxia 3 and should be better evaluated

Noorasyikin MA, Azizan EA, Teh PC, Farah Waheeda T, Siti Hajar MD, Long KC, et al.

Parkinsonism Relat Disord, 2020 01;70:42-44.
PMID: 31841943 DOI: 10.1016/j.parkreldis.2019.12.007
LBOS 02-06 HISTOPATHOLOGICAL-SPECIFIC MUTATION SPECTRUM OF ALDOSTERONE-PRODUCING ADENOMAS

Azizan E, Sukor N, Kamaruddin NA, Jamal AR, Ceral J, Solar M, et al.

J Hypertens, 2016 Sep;34 Suppl 1 - ISH 2016 Abstract Book:e550.
PMID: 27754305

Aldosterone-producing adenoma (APA) is a common curable cause of hypertension. Somatic mutations in five genes (KCNJ5, ATP1A1, ATP2B3, CACNA1D, and CTNNB1) have been found to cause the excess aldosterone production of two thirds of APAs [1-4]. KCNJ5 mutant APAs, the most common and largest, had explicit genotype-phenotype relationship - a low protein expression of KCNJ5 relative to their peritumoural zona glomerulosa (ZG) and a zona fasciculata-like composition [5-6]. Conversely for the other genes, controversy arises on whether they have the opposite cell phenotype [4,7-8]. This prospective study aim to to characterize the histopathological-specific mutation spectrum of APAs.
[OP.3A.01] THE COMPARISON OF THE TRANSCRIPTOME PROFILE OF THE AUTONOMOUS AND THE PHYSIOLOGICAL ALDOSTERONE-PRODUCING TISSUE, THE ALDOSTERONE-PRODUCING ADENOMA AND THE ZONA GLOMERULOSA

Zhou J, Lam BY, Neogi SG, Yeo GS, Teo AE, Maniero C, et al.

J Hypertens, 2016 Sep;34 Suppl 2:e26.
PMID: 27508643 DOI: 10.1097/01.hjh.0000491398.48468.bf

Primary aldosteronism (PA) is the most common type of secondary hypertension occurring in ∼10% of hypertensive patients. Up to 50% of PA is caused by aldosterone-producing adenomas (APA). We recently performed a microarray assay using 21 pairs of zona glomerulosa (ZG) and zona fasciculata (ZF), and 14 paired APAs. This study is to identify the potential biological processes and canonical pathways involved with aldosterone regulation, APA formation, or APA and ZG cell functions.
Fulltext Frequency of Spinocerebellar Ataxia type 1, 2, 3,6 and 7 and clinical profile of Spinocerebellar Ataxia type 3 in Malaysia

Mohamed Ibrahim N, Lau YH, Ariffin N, Md Desa SH, Azizan E, Chin LK, et al.

Cerebellum & ataxias, 2020;7:11.
PMID: 32922823 DOI: 10.1186/s40673-020-00120-2

Spinocerebellar ataxias (SCA) are highly heterogenous group of neurodegenerative diseases causing progressive cerebellar dysfunction. We report the first description of relative frequencies of the common SCA mutations and of phenotypic characteristics of SCA3 patients among Malaysians. Pooled data from adult Malaysian patients who had undergone genetic testing for SCA 1,2,3,6 and 7 at UKM Medical Centre and Institute for Medical Research from 2017 to 2020 were analysed. Fifteen patients with SCA 3 had detailed clinical phenotype evaluation using Inventory for Non -Ataxia Signs (INAS) and Ataxia Severity evaluation using the Scale for Assessment and Rating of Ataxia (SARA). Out of 152 adults patients who were tested for common SCA mutations, 64(42.1%) patients were tested positive for either SCA 1,2,3,6 or 7. Of the 64 positive cases, 44 (68.9%) patients were diagnosed with SCA 3 followed by SCA 2 in 13(20.3%) patients and SCA 1 in 5 (7.8%) patients. Our findings suggest that Malay race had the highest frequency of SCA (n = 34, 50%), followed by the Chinese (n = 16, 23.5%) and approximately 60 (93.8%) SCA patients had first degree family history. In conclusion, SCA 3 is the commonest SCA in Malaysia, followed by SCA 2 and SCA 1. It is important to develop a proper registry of SCA patients to further understand the true prevalence and local impact of the disease in Malaysia.