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Professor Mohd Zaki Salleh | E-mail: zakisalleh@puncakalam.uitm.edu.myIntegrative Pharmacogenomics Institute (iPROMISE)Universiti Teknologi MARA

M E D I C I N E

Genetic studies on Malaysia’s Orang Asli peoples could lead to tailored medical advice that is more appropriate for their unique makeup.

Investigations into the health of indigenous Orang Asli peoples in Malaysia suggest that changes of lifestyle and modernization have increased their risks of cardiovascular disease and diabetes. Genetic analyses also show that they have a lower metabolic capacity, requiring lower doses of many common painkillers. Taken together, researchers believe that better prevention and education programs are needed, along with the implementation of precision medicine in the Orang Asli.

The Orang Asli, or ’first people’ of Peninsular Malaysia, comprise less than 1% of the Malaysian population. Despite some snapshots of their health, there is not a great deal of medical information on these tribes, several of which are categorized as fragile.

Since the late 1950s, the Government of Malaysia, along with non-government agencies, has tried to bring advancement and improve the quality of life in these communities, but they are still reported to have lower health status compared to other ethnic groups on the peninsula. The average life expectancy of the Orang Asli is 54 years for females and 52 for males.

Mohd Zaki Salleh, Lay Kek Teh and colleagues of the Universiti Teknologi MARA have conducted medical examinations and biochemical analyses, which they report in BMC Public Health. They observed lower total cholesterol than in the control population of urban Malays. But their HDL—the good cholesterol that acts to clear LDL, the bad cholesterol, away from the arteries—was lower, conferring a greater risk of cardiovascular disease. Higher insulin levels were observed in many of the tribes and this, alongside higher fasting plasma glucose levels, suggests an increased risk of diabetes.

The team also characterized CYP2C9 gene variants that metabolize a range of drugs, from warfarin and phenytoin to non-steroidal anti-inflammatory drugs like aspirin and ibuprofen. They show, in a study published in Drug Metabolism and Pharmacokinetics, that large numbers of the Orang Asli are likely to have reduced metabolic capacity and therefore would require a lower dose of drugs that are metabolized by CYP2C9.

A lack of understanding of this could lead to drug failure or problems with toxicity at normal dosage levels. The researchers believe this work is important in delivering precision medicine to these tribes. Combining this knowledge with improving education and messages around lifestyle and disease prevention could lead to better strategies and healthier communities in these vulnerable groups.

IMPROVING THE HEALTH OF FRAGILE TRIBES IN MALAYSIA

Did you know? In 2008 there were only 178,963 Orang Asli in Malaysia compared to the general population of 27.3 million.

Professor Lay Kek Teh | E-mail: tehlaykek@puncakalam.uitm.edu.myIntegrative Pharmacogenomics Institute (iPROMISE)Universiti Teknologi MARA

Credit: LRGS Evolutionary Genomics Orang Asli, MOHE, UiTM, USM & UKM

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Screening patients for a gene variant before starting epilepsy treatment could reduce the incidence of life-threatening drug reactions.

Drug-induced hypersensitivity reactions (DIHRs) are serious and life threatening. A common example is the use of the antiepi-leptic drug carbamazepine, but the mech-anisms that trigger it are unclear. Current scientific consensus holds that people who have a specific variation of the ‘human leukocyte antigen B’ (HLA-B) gene, which provides the code for making a protein that plays a critical role in the immune system, are more at risk of DIHR. However, the mechanism linking this gene to DIHR is currently unknown. As this specific variation, called HLA-B*15:02, is fairly common in people of South-East Asian descent, this is a serious problem for clinicians in the region.

Researchers at Universiti Teknologi MARA Selangor in Malaysia used com-puter modelling to mimic and analyse how the protein encoded by HLA-B*15:02 interacts with a range of antiepileptic medications. The researchers used various software to mimic how drugs interact with a specific region of the HLA protein that is crucial for its normal functionality. Since the HLA complex acts like a sort of identity card in our cells, anything inter-acting with it other than our own immune cells can cause problems.

Carbamazepine and another eight out of 26 antiepileptic drugs (AEDs) that were tested were found to bind strongly to the

HLA complex in the simulation model. The team believes this strong binding is behind DIHRs in patients who carry the variant gene.

The remaining AEDs that did not show strong binding interactions with the HLA-B*15:02 complex, including clonaz-epam, nitrazepam and stiripentol, could be safer options for patients that have already developed adverse reactions to other antiepileptic drugs.

Testing for HLA-B*15:02, which can be done in as few as four hours, should be incorporated into clinical practice as soon as possible, recommends the study’s lead researcher Mohd Zaki Salleh.

THE GENE THAT TURNS EPILEPSY TREATMENT DEADLY

Did you know? Drug responses are known to vary based on the genetic profiles of patients. This is why personalized medicine is highly desirable to prevent adverse effects. Research-ers are working on developing diagnostic tools to determine more effective and safer medications and doses that are tailored based on the variations in patients’ genes.

Professor Mohd Zaki Salleh | E-mail: zakisalleh@puncakalam.uitm.edu.my Integrative Pharmacogenomics Institute (iPROMISE)

Universiti Teknologi MARA

M E D I C I N E

Professor Lay Kek Teh | E-mail: tehlaykek@puncakalam.uitm.edu.myIntegrative Pharmacogenomics Institute (iPROMISE)

Universiti Teknologi MARA

The image shows how researchers predict AEDs (the multicolour sticks) bind to the HLA complex (pale green and grey plus magenta-coloured peptide).

Credit m

ain image: lightw

ise / 123rfC

redit: Universiti Teknologi M

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Although the Islamic finance industry is growing at a rapid rate, researchers have highlighted areas of governance that must be reformed.

In 2007, the market price of Islamic- compliant bonds – or sukuk – fell sharply after Taqi Usmani of the Accounting and Auditing Organization for Islamic Finance

Institutions, a regulatory body in Bahrain, said that 85% of the bonds were not com-pliant with Islam’s sharia laws, highlighting growing concerns over the governance of Islamic finance.

A decade later, the industry is growing at a rapid rate and its products and ser-vices are widely offered across the world. According to the Malaysia International Islamic Financial Centre, the industry had assets of US$2.1 trillion at the end of 2015 and saw a compounded annual growth rate of 17.3% between 2009 and 2014.

Islamic financial institutions (IFIs) offer the same products as western banks with the big difference that sharia finance must be free from interest, gambling and invest-ment in prohibited items.

This means that as well as dealing with conventional risk, IFIs need a sharia gover-nance framework to ensure their practice of Islamic finance follows the tenets, condi-tions and principles propagated by Islam.

However, researchers at Universiti Teknologi MARA, the International Islamic University in Malaysia and Humber Col-lege in Canada have found that issues may arise in governance systems — through which institutions ensure there is effective independent oversight of sharia — that leave IFIs open to sharia-related risk.

One area of concern is that there are four different Islamic legal schools of thought. Since they have different opinions on the same issues, this can lead to variation in the way Islamic finance is structured. On the other hand, this difference in opinions can be positive; Islam has not restricted society to follow only one school of thought if it does not involve the fundamentals.

Even so, this can result in ‘fatwa fishing’, whereby someone chooses between the available schools of thought and picks the one that best meets their immediate need.

Another problem is that different insti-tutes have varying standards and practices. For example, Bahrain has both a sharia governance committee at an institutional level and a sharia advisory board at a national level, whose role is limited to advising the central bank.

Lead researcher Nawal Kasim from Universiti Teknologi MARA

says that higher sharia authorities may not be effective if they focus too much on the regular controlling compliance for IFIs, resulting in negative impacts on the stability of the Islamic finance industry.

“If these practices are prolonged, there is no point to Islamic finance and it defeats the purpose of the emergence of IFIs,” she says.

The researchers urge IFIs to pay more atten-tion to tackling sharia risk management in order to address legal, reputational and liquidity risks.

They recommend that sharia committee members become actively involved in moni-toring the operations of IFIs and that members be liable for breach of contract and negligence.

They also call on IFIs to make disclosures on sharia governance to complement the re-quirement of conventional governance codes such as the International Financial Reporting Standards and the Generally Accepted Accounting Principles. Another recom-mendation is to incorporate the findings of sharia audits to add value to the annual reports of IFIs.

“These defects should be rectified soon, or else IFIs will end up with the possibility of bad reputations and losses,” Salman says.

STRENGTHENING THE GOVERNANCE OF ISLAMIC BANKS

Associate Professor Dr Nawal Kasim | E-mail: nawal120@salam.uitm.edu.myAccounting Research Institute Universiti Teknologi MARA, Malaysia

P E O P L E

Credit: Piotr Pawinski / 123rf6 6

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