Sys Rev Pharm 2020;11(9):627-631 A multifaceted review journal in the field of pharmacy 627 Systematic Reviews in Pharmacy Vol 11, Issue 9, Sep-Oct 2020 Genotype of Potassium Inwardly Rectifying Channel, Subfamily J, Member 11 (KCNJ 11) Gene and Glycaemia Control in Diabetic Patients: A Narrative Review Dyah Aryani Perwitasari a* , Imaniar Noor Faridah a , Haafizah Dania a , Lalu Muhammad Irham a , Fathia Vikri Salsabila a , Rita Maliza b a Faculty of Pharmacy, Universitas Ahmad Dahlan, Jl Prof Dr Soepomo, Janturan, Yogyakarta, 55164, Indonesia b Faculty of Science and Applied Technology, Universitas Ahmad Dahlan, Kampus Utama, Jl Jend A Yani, Yogyakarta, Indonesia *Corresponding author: Dyah Aryani Perwitasari Email: dyah.perwitasari@pharm.uad.ac.id ABSTRACT There are several factors that may affect the body response to the medicine and the drug response. One of the factors is the genetic variations. Some genes are predicted to have significant roles in oral antidiabetic response. This review is intended to define the role of Potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) genotypes to the glycemia control in Diabetes melitus type 2 (DMT2) patients. We conducted literature review using keywords “genotype description, kcnj11 gene, blood sugar level, diabetes melitus type 2” in Pubmed, Science Direct, BMC, PMC and Google Scholar database. Among the fourteen articles, we found that the most alleles studied was: rs5219 and rs5215. The homozygous wildtypes of rs5219 have no correlation with the risk of DMT2. However, the correlation between the allele of rs5219 and the medication response are still unclear. Furthermore, the correlation of alleles of rs5215 and the risk of DMT2 and medication response are still contradictive. The future studies are still needed to confirm the correlation between allele of rs5219, rs5215 and the risk of DMT2 and medication response. Keywords: Provide KCNJ11, Diabetic, medication, response Correspondence: Dyah Aryani Perwitasari Faculty of Pharmacy, Universitas Ahmad Dahlan, Jl Prof Dr Soepomo, Janturan, Yogyakarta, 55164, Indonesia Email: dyah.perwitasari@pharm.uad.ac.id INTRODUCTION Diabetes melitus type 2 (DMT2) is the metabolic disturbance indicated with the increase of Blood Sugar Level (BSL) due to the insulin resistance (1). DMT2 caused the sixth of death in the world in 2016 (2). The number of DMT2 in Indonesia is getting increase yearly and will reach 21.3 juta penduduk pada tahun 2030 (3). Genetic studies are needed of define the risk factor of genetic in DMT2. The results of genetic studies can be used to design prevention strategic and treatment (4). The Genome Wide Association Study (GWAS) reported some genes as the risk factors of DMT2, such as: ABCC8, KCNJ11, PPARγ, UII, TCF7L2, CDKAL1, CDKN2A/B, IGF2BP2, HHEX/IDE, FTO, dan SLC30A8(5–9). One of the gene associated with DMT2 is potassium inwardly rectifying channel (KCNJ11). This gen has a role in the expression of Kir6.2, the subdomain of integrated protein KATP channel, β pancreatic cell with the function of K + selective membrane (4). The KCNJ11 expressed the K+ ion channel which sensitive to the ATP and has significant role in controlling the insulin secretion (10). The polymorphism of KCNJ11 related to rs5219, describes the substitution of glutamate to lysine which can cause the decrease sensitivity of KATP. This situation can open the channel more frequent and inhibit the insulin secretion (11)(12). Some previous studies found that genes variation can be the risk factor of DMT2 and some are associated with the glycaemic control (9,12). The aim of this narrative review is to describe the role of KCNJ11 gene as the risk factors of DMT2 and its association with the glycaemia control. MATERIAL AND METHODS Materials We found 5.290 articles from PubMed (446), Google Scholar (4.202), Science Direct (59), DOAJ, BioMed Central (44), dan Europe PMC (529) that were accessed during June 2020. After the critical appraisal, we identified 14 articles relevant to the topic. The study outcomes were Fasting Blood Glucose (FBG), Blood Sugar Level (BSL) and HbA1C (Hemoglobin A1c). METHOD This review used a narrative review. The articles were found from PubMed, Science Direct, and Google Scholar. The inclusion criteria for the articles were full text articles and published from 2010 to 2020. Exclusion criteria was no genotype variations discussed in the article. The PICO were "Genotype Description" AND "KCNJ11 gene" OR "ABCC8" AND “Blood Sugar Level" OR Diabetes Mellitus Type 2. From the 5290 articles, we extracted 3797 articles due to the year limitation (2010-2020). The next procedures were selecting the articles based on the review objective and we got 29 articles. After the critical appraisal, we identified 14 articles met the criteria (Table 1). RESULTS AND DISCUSSION We found 15 articles which conducted in Egypt, Syrian, Mexico, Gaza, Russia, Iran, Kirgizstan and Indonesia. Table 2 shows the results of articles review. All of the studies are original articles with 9 studies of case control, 4 studies of RCT and 1 study of cross-sectional design. The total number of subjects participated in all studies were 3918, with 3129 among them are the DMT2 patients and the rests were subjects in control groups. We identified these SNPs; rs5219 (E23K dan Glu23Lysy), rs5218 (A190A), rs5216 (L267L), rs1800467 (L270V) and rs5215 (I337V). The study of Gonen et al, 2012 in Turkish population, shows that the CC genotype of L5216, GA genotype of E23K, CC genotype of L267L and AA genotype of I337V are dominantly found in the case group. In the case group, the frequency of heterozygous and homozygous mutant is high (13). The study of Abed et al, 2013, in Gaza population, presents that KK genotype has high proportion in case