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@#Introduction: Risk factors for type 2 diabetes mellitus (T2DM) include obesity and some genetic factors. Obesity involves mild chronic inflammation that predisposes cells to insulin resistance. Two genes that influence obesity and insulin resistance are Proconvertase-1 (PC-1) and resistin (RETN). PC-1 affects the activation of hormones that regulate satiety and hunger. Resistin is one of the inflammatory factors that influence the occurrence of insulin resistance. This study aimed to determine the influence of polymorphism in the PC-1 gene rs1044498 (C>A) and resistin gene RETN + 299 G>A rs3745367 on the risk of diabetes in obese Papua population. Methods: This study involved 58 obese people with T2DM and 58 obese people without DM. We examined the characteristics of blood pressure, lipid profile and insulin resistance by HOMA-IR. The genes examined were PC-1 rs1044498 (C>A) and RETN+ 299 G>A rs3745367 by the PCR-RFLP method. The relationship of gene variations with biochemical parameters was determined with analysis of variance. The results were considered significantly different if P < 0.05. Results: In this study, parameters of diastolic blood pressure, triglycerides and insulin resistance were higher while high density lipoprotein (HDL) levels were lower and significantly different in the obese with T2DM group compared to the obese only group. The carrier of the A allele in the PC-1 gene rs1044498 was higher in the obese group than the obese with T2DM but not significantly different in biochemical parameters. Carrier of the AA genotype in the RETN gene + 299 G>A rs3745367 had higher triglycerides and HOMA-IR and lower HDL levels significantly different (P<0.05) than other genotypes in the obesity with T2DM group. Conclusion: PC-1 rs1044498 gene was a risk factor for obesity but not for T2DM, while RETN gene rs3745367 was a risk factor for dyslipidemia and diabetes in obese people in the Papua population.
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@#Background: Interleukin-6 (IL-6) and C-Reactive Protein (CRP) are mediators of inflammatory responses and increase in people who are obese . The increase of IL-6 and CRP levels is modified by polymorphism of -174 G>C IL-6 gene. Aim: The purpose of this study was to investigate the relationship between -174 G>C IL-6 polymorphism gene on the level of IL-6 and CRP in the population of western Indonesia obese who are obese. Methods: In this study, we examined 178 subjects consisting of 89 who are obese with BMI> 25, and controls with BMI between 18.5 and 23. Fasting blood was taken from each subject for the examination of IL-6 and CRP levels by the ELISA method. Determination of genotype -174 G>C IL-6 gene was examined by Polymerase Chain reactionRestriction Fragment Length Polymorphism (PCR-RFLP) methods. Results: The results of this study showed increased levels of IL-6 and CRP in the obese group compared to the controls. In the obese group, CC genotype had higher CRP and lower IL-6 levels than the GC and GG genotypes. The frequency of CC genotype in the obese group was 47.2% compared with 28.1% in controls and this genotype was considered a risk factor for obesity. Carriers of the C genotype as a dominant or a recessive model had greater risk of obesity. Conclusion: It was concluded that the polymorphism - 174G>C IL-6 gene is a risk factor for obesity and is associated with increased levels of IL-6 and CRP in an obese group of the Western Indonesian ethnic population.
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OBJECTIVES: The CYP2B6 is one of the most polymorphic CYP genes in humans that has the potential to modify the pharmacological and toxicological responses to clinically important drugs such as antimalarial artemisinin and its derivatives. The aim of the study was to determine the frequency of CYP2B6 polymorphisms in Timor malaria endemic area, East Nusa Tenggara, Indonesia where Artemisin-based Combination Therapy (ACT) has been used to treat uncomplicated malaria. METHODS: A total of 109 healthy subjects were participated in this study. CYP2B6*4, *6 and *9 polymorphisms were analyzed using PCR-RFLP to confirm the SNPs prevalence of 516G>T and 785A>G in exon 4 and 5. RESULTS: There were 96 subjects included in the analysis. In the exon 4 of CYP2B6 516G>T, the frequency of the T mutation was 37.5% (39/96), and the wildtype 27.1% (26/96). In the exon 5, CYP2B6 785A>G mutant was detected in 29.2% (28/96) of individuals, and the wildtype allele in 35.4% (34/96). The frequency of CYP2B6*9 (516G>T), CYP2B6*4 (785A>G) and CYP2B6*6 (516G>T and 785A>G) were 40.6%, 29.2% and 22.9%, respectively. The prevalence of these CYP2B6 gene polymorphisms in Timorian ethnic were higher than that in Malay, Han Chinese, Indian, and Egyptian populations. CONCLUSION: The prevalence of these CYP2B6 516G>T and 785A>G polymorphisms in Timorian ethnic is higher than that in other populations. These polymorphisms may affect the metabolism of artemisinin and its derivatives.
Subject(s)
Humans , Alleles , Asian People , Cytochrome P-450 CYP2B6 , Exons , Healthy Volunteers , Indonesia , Malaria , Metabolism , Polymorphism, Single Nucleotide , PrevalenceABSTRACT
Objective/background: Thalassemia is a monogenic hematologic disease that has the highest prevalence globally. In addition, there is complexity of the genetic background associated with a variety of phenotypes presented among patients. Genetic heterogeneity related to fetal hemoglobin [HbF] production has been reported as an influencing phenotypic factor of beta-thalassemia [beta-thal]. Therefore, this study aimed to find the effect of these genetic modifiers, especially in the XmnI locus, rs11886868, rs766432 [BCL11A], and rs9399137 [HBS1L-MYB], among beta-thal and HbE/beta-thal patients in Indonesia, according to laboratory and clinical outcomes, including HbF levels and clinical scores. This study was also designed to compare these modifying effects among beta-thal and HbE/beta-thal patients in Indonesia
Methods: A total of 189 patients with genotyping of beta-thal and HbE/beta-thal were included in this study. The erythrocytes index and Hb electrophoresis measurements were calculated using appropriate methods. The severity of beta-thal and HbE/beta-thal was classified based on the Mahidol score. Polymorphism of the XmnI locus, rs11886868, rs766432 [BCL11A], and rs9399137 [HBS1L-MYB] was determined using polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] and amplification refractory mutation system [ARMS] methods
Results: The distributions of minor allele in the XmnI locus, rs11886868, rs766432, and rs9399137 were 14%, 22%, 19% and 18% respectively. The variation allele in the XmnI locus, rs11886868, and rs766432 showed a significant value for modifying HbF and clinical score in HbE/beta-thal patients, but rs9399137 did not demonstrate such features. In beta-thal patients, however, no correlation was found for any single-nucleotide polymorphisms and clinical appearance
Conclusion: The XmnI locus, rs11886868, and rs766432 have a modifying effect on HbF and clinical score in HbE/beta-thal patients in Indonesia, but not in beta-thal patients