Hypertension or high blood pressure is a health problem that is increasingly common throughout the world, including in Indonesia. The number of individuals suffering from hypertension continues to increase from year to year. According to the 2018 Riskesdas data, around 1 in 3 adults in Indonesia suffer from hypertension, and this figure is higher than the 2013 data. Unfortunately, many people do not know that they suffer from hypertension. Around 46% are not aware of it, and only 42% have been diagnosed by medical personnel. In developing countries such as Indonesia, hypertension treatment still faces many challenges, especially in choosing the most appropriate drug.
Individual responses to blood pressure-lowering drugs can vary depending on ethnicity, for example, between Melanesian and non-Melanesian groups in Indonesia. Research conducted on Melanesian and non-Melanesian communities in Indonesia shows that the response to one type of blood pressure-lowering drug, namely Lisinopril, can be different. In a 2015 study in Jayapura, individuals with hypertension who had never been treated received Lisinopril therapy at a dose of 5 mg. The participants’ blood pressure was measured at baseline and re-evaluated after taking the drug for 4 weeks. The results showed that the non-Melanesian group experienced a greater decrease in blood pressure than the Melanesians.
Systolic blood pressure (the top number) dropped by about 34.5 mmHg in the non-Melanesians, while in the Melanesians it only dropped by about 24.5 mmHg. Likewise, diastolic blood pressure (the bottom number) decreased more in the non-Melanesians. This difference suggests that there are other causes that can affect how this drug works in each group, one of which is genetic factors. To date, there has not been much research examining how differences in genes in the body and the influence of regulators outside of genes in the form of microRNAs can affect the action of Lisinopril, especially in Melanesians in Indonesia. Therefore, further research is needed that looks deeper, not only from the blood chemistry side, but also from the gene side and the mechanism outside the gene.
This study aims to determine the effect of microRNA expression, namely microRNA-133 and microRNA-155, differences in one-point changes in the Renin, ACE1, and Angiotensinogen genes, and levels of proteins that regulate blood pressure such as ANG-II, ACE-1, and Renin in the blood that are associated with differences in response to Lisinoril administration in hypertensive patients from the Melanesian group in Jayapura. It is hoped that this study can help explain why drug effects can differ between ethnic groups, and become the basis for more appropriate treatment for each individual based on their genetic profile. “Our study found that individuals from the Melanesian group experienced a smaller decrease in blood pressure after taking Lisinopril compared to the non-Melanesian group.
When examined, no significant differences were found in the gene sections related to blood pressure regulation, such as the Renin, ACE, and Angiotensinogen genes. However, we found significant differences in microRNA. After being given Lisinopril, the Melanesian group showed higher miR-133 and miR-155 expression compared to the non-Melanesian group. This increase in miR-133 may occur because the body tries to suppress the Angiotensinogen gene so that the production of Angiotensin-II is reduced. Meanwhile, the increase in miR-155 is likely triggered by the death of blood vessel cells due to a decrease in blood pressure that is not too large. Interestingly, miR-133 showed an inverse relationship with Angiotensin-II protein levels in these two groups, while miR-155 was related to blood pressure differently between the Melanesian and nonMelanesian. This provides new insights into the potential of miR-133 and miR-155 as biomarkers in individuals with hypertension, to predict the occurrence of effects on the heart and blood vessels.