Endometrial receptivity defects MUC-1 and COX-2 polymorphisms in endometriosis.

The endometrium produces MUCIN-1 (MUC-1) and cyclooxygenase-2 (COX-2), which are essential for implantation. MUC-1 is required for adhesion, while COX-2 is necessary for decidualization. Variations or polymorphisms in MUC-1 and COX-2 can lead to changes in endometrial receptivity. This study investigated the relationship between MUC-1 and COX-2 polymorphisms and endometrial receptivity in endometriosis patients. Blood DNA samples were collected from 35 patients with endometriosis and 32 healthy patients between days 19 to 24 of their menstrual cycle (secretory phase). MUC-1 polymorphism was determined using the Amplification Refractory Mutation System (ARMS), and COX-2 gene polymorphism was assessed using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). The frequency distribution of gene polymorphisms between the two groups was compared using bivariate analysis. There were seven genotypic combinations of MUC-1 and COX-2: AAGC; AAGG; GACC; GAGC; GAGG; GGGC; GGGG. The AAGC genotype combination test was significant, with an OR=6.43 (95% CI:1.09-7.62) and p=0.01. In conclusion, combining MUC-1 and COX-2 (AAGC) genotypes results in endometrial receptivity defects in endometriosis.

Clinical characterizations of three adults with genetically confirmed spinal muscular atrophy: a case series.

BACKGROUND: Spinal muscular atrophy is a recessively inherited autosomal neuromuscular disorder, with characteristic progressive muscle weakness. Most spinal muscular atrophy cases clinically manifest during infancy or childhood, although it may first manifest in adulthood. Although spinal muscular atrophy has come to the era of newborn screening and promising treatments, genetically confirmed spinal muscular atrophy patients are still rare in third world countries, including Indonesia. CASE PRESENTATIONS: We presented three Indonesian patients with spinal muscular atrophy genetically confirmed during adulthood. The first case was a 40-year-old male who presented with weakness in his lower limbs that started when he was 9 years old. At the age of 16 years, he could no longer walk and started using a wheelchair. He first came to our clinic at the age of 38 years, and was diagnosed with spinal muscular atrophy 2 years later. The second patient was a 58-year-old male who presented with lower limb weakness since he was 12 years old. Owing to the geographical distance and financial problems, he was referred to our clinic at the age of 56 years, when he already used a walker to walk. Lastly, the third patient was a 28-year-old woman, who was in the first semester of her second pregnancy, and who presented with slowly progressing lower limb weakness. Her limb weakness began at the age of 8 years, and slowly progressed until she became dependent on her wheelchair 8 years later until now. She had successfully given birth to a healthy daughter 3 years before her first visit to our clinic. All three patients were diagnosed with neuromuscular disorder diseases, with the differential diagnoses of Duchenne muscular dystrophy, spinal muscular atrophy, and Becker muscular dystrophy. These patients were finally confirmed to have spinal muscular atrophy due to SMN1 deletion by polymerase chain reaction and restriction fragment length polymorphism. CONCLUSIONS: Many genetic diseases are often neglected in developing countries owing to the difficulty in diagnosis and unavailable treatment. Our case series focused on the disease courses, diagnosis difficulties, and clinical presentations of three patients that finally lead to diagnoses of spinal muscular atrophy.

The PPARGC1A Is the Gene Responsible for Thrifty Metabolism Related Metabolic Diseases: A Scoping Review.

The "thrifty genotype" hypothesis has thus far described the relationship between specific genes and the population's resilience to food scarcity circumstances, but its link to the widespread prevalence of genetic diseases and metabolic syndrome has not been adequately mapped. The purpose of the study was to discover genes responsible for thrifty metabolism. A systematic search with keywords was performed for relevant titles. This study used the article's database published by Pubmed, Proquest, and EBSCO from January, 2009 to September, 2022. Out of 418 papers screened for eligibility, the final evaluation determined that five studies should be included in the analysis. Results indicated that PPARGC1A Gly482Ser led to high BMI in the Tongans population but was unrelated to the onset of type 2 diabetes mellitus, but this was not the case in the Maori population. Significantly differing frequencies of PPAR C1431T and Pro12Ala gene polymorphisms were observed in the Iranian population. GWAS identification of additional genes in Asian and European populations did not produce consistent findings. As a summary, PPARGC1A Gly482Ser addresses as the gene responsible for thrifty metabolism in the Pacific population although some studies show inconsistent results.

Standardised Ethanol Extract of Tithonia diversifolia (Hemsley) A Gray Leaves Improve Insulin Sensitivity and Increase Mitochondrial DNA Copy Numbers in Skeletal Muscles of Streptozotocin-Nicotinamide-Induced Rats.

Background: In this study, we examined the anti-diabetic activity of standardised extracts of Tithonia diversifolia (Hemsley) A Gray (T. diversifolia) leaves for their effects on insulin resistance and mitochondrial DNA (mtDNA) copy number. Methods: T. diversifolia leaves were extracted using an ultrasound-assisted method and standardised using Tagitinin C. There were six groups: i) normal control; ii) diabetic group; iii) metformin group (300 mg/kg) and iv) groups treated with three different doses of extract (50 mg/kg, 100 mg/kg and 150 mg/kg). Blood samples were taken before and after 28 days of treatment for fasting plasma glucose (FPG) and insulin analysis, which were used for a Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) calculation. The soleus and gastrocnemius muscles were harvested after 28 days of treatment for the measurement of mtDNA copy number. Results: The results showed an improvement in blood glucose levels and HOMA-IR scores in all treatment groups. The results of mtDNA copy number analysis also revealed significant improvement with the highest number observed at an extract dose of 100 mg/kg in which the mtDNA copy number increased up to 3 times in the soleus muscles (P < 0.001). Conclusion: T. diversifolia extract has the potential to be used as an anti-diabetic agent that improves insulin resistance, possibly by increasing mtDNA content.

The influence of metformin transporter gene SLC22A1 and SLC47A1 variants on steady-state pharmacokinetics and glycemic response.

Interindividual variation is important in the response to metformin as the first-line therapy for type-2 diabetes mellitus (T2DM). Considering that OCT1 and MATE1 transporters determine the metformin pharmacokinetics, this study aimed to investigate the influence of SLC22A1 and SLC47A1 variants on the steady-state pharmacokinetics of metformin and the glycemic response. This research used the prospective-cohort study design for 81 patients with T2DM who received 500 mg metformin twice a day from six primary healthcare centers. SLC22A1 rs628031 A>G (Met408Val) and Met420del genetic variants in OCT1 as well as SLC47A1 rs2289669 G>A genetic variant in MATE1 were examined through the PCR-RFLP method. The bioanalysis of plasma metformin was performed in the validated reversed-phase HPLC-UV detector. The metformin steady-state concentration was measured for the trough concentration (Cssmin) and peak concentration (Cssmax). The pharmacodynamic parameters of metformin use were the fasting blood glucose (FBG) and glycated albumin (GA). Only SLC22A1 Met420del alongside estimated-glomerular filtration rate (eGFR) affected both Cssmax and Cssmin with an extremely weak correlation. Meanwhile, SLC47A1 rs2289669 and FBG were correlated. This study also found that there was no correlation between the three SNPs studied and GA, so only eGFR and Cssmax influenced GA. The average Cssmax in patients with the G allele of SLC22A1 Met408Val, reaching 1.35-fold higher than those with the A allele, requires further studies with regard to metformin safe dose in order to avoid exceeding the recommended therapeutic range.

NKX2-5 variants screening in patients with atrial septal defect in Indonesia.

BACKGROUND: NKX2-5 variant in atrial septal defect patients has been reported. However, it is not yet been described in the Southeast Asian population. Here, we screened the NKX2-5 variants in patients with atrial septal defect (ASD) in the Indonesian population. METHOD: We recruited 97 patients with ASD for genetic screening of the NKX2-5 variant using Sanger sequencing. RESULTS: We identified three variants of NKX2-5: NM_004387.4:c.63A>G at exon 1, NM_004387.4:c.413G>A, and NM_004387.4:c.561G>C at exon 2. The first variant is commonly found (85.6%) and benign. The last two variants are heterozygous at the same locus. These variants are rare (3.1%) and novel. Interestingly, these variants were discovered in familial atrial septal defects with a spectrum of arrhythmia and severe pulmonary hypertension. CONCLUSION: Our study is the first report of the NKX2-5 variant in ASD patients in the Southeast Asian population, including a novel heterozygous variant: NM_004387.4:c.413G>A and NM_004387.4:c.561G>C. These variants might contribute to familial ASD risk with arrhythmia and severe pulmonary hypertension. Functional studies are necessary to prove our findings.

Correlation of serum electrolytes with serial miRNA in advanced stage non-small cell lung cancer (NSCLC) in Indonesia.

OBJECTIVE: This study aims to evaluate the correlation between electrolytes and serial miRNAs from our previous study. We want to prove that there is the molecular basis that underlying electrolytes disturbances as the predictive indicator to the outcome in NSCLC patients. RESULTS: There were positive correlation between potassium level with miR-34 (p = 0.008, r = 0.366), miR-148 (p = 0.004, r = 0.394) and miR-155 (p = 0.031, r = 0.300).

Influence of Single Nucleotide Polymorphism of ENPP1 and ADIPOQ on Insulin Resistance and Obesity: A Case-Control Study in a Javanese Population.

Single nucleotide polymorphisms (SNPs) in obesity-related genes, such as ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) and adiponectin (ADIPOQ), potentially increase the risk of insulin resistance, the most common metabolic dysregulation related to obesity. We investigated the association of ENPP1 SNP K121Q (rs1044498) with insulin resistance and ADIPOQ SNP + 267G > T (rs1501299) with circulating adiponectin levels in a case-control study involving 55 obese and 55 lean Javanese people residing in Yogyakarta, Indonesia. Allele frequency was determined by a chi squared test or Fisher's exact test with an expected value less than 0.05. Odds ratios and 95% confidence intervals were estimated by regression logistic analysis. The presence of the Q121 allele of ENPP1 resulted in significantly higher fasting glucose, fasting insulin levels, and HOMA-IR, as compared to homozygous K121 carriers. The risk of insulin resistance was elevated in obese individuals carrying Q121 instead of homozygous K121. Adiponectin level was significantly lower in the obese group as compared to the lean group. Obese individuals carrying homozygous protective alleles (TT) of ADIPOQ tended to have lower adiponectin levels as compared to GT and GG carriers, however, we did not find statistically significant effects of the +276G > T SNP of the ADIPOQ gene on the plasma adiponectin levels or on the development of obesity.

Polyherbal formula (ASILACT®) induces Milk production in lactating rats through Upregulation of α-Lactalbumin and aquaporin expression.

BACKGROUND: Polyherbal formula (PHF) contains extract of Sauropus androgynous (L.) Merr., Trigonella foenum-graceum L., and Moringa oleifera Lam. considered to induce galactagogue activity. This research aimed to evaluate the galactagogue activity of PHF and its effects on α-lactalbumin (LALBA) as well as aquaporin (AQP) gene expression at messenger ribonucleic acid (mRNA) levels in mammary glands of lactating rats. METHODS: Thirty lactating Wistar rats were randomly divided into five groups (n = 6), each has 7 pups. Group I was treated orally with distilled water as negative control. Groups II, III, and IV were orally administered with PHF at 26.25, 52.5 and 105 mg/kg/day, respectively. Group V was treated with domperidone 2.7 mg/kg/day, orally as positive control. The treatment was performed at third day until fifteenth day of parturition. The observed parameters include the galactagogue activity indicating by milk yield of lactating rats, the pup weight changes and lactating rats body weight changes during lactating period, mRNA expression of LALBA and AQP using quantitative Real Time Polymerase Chain Reaction (qRT-PCR) and histopathological analysis of mammary glands at the end of treatment period. RESULT: The result showed that the PHF groups (52.5 and 105 mg/kg/day) and domperidone were significantly increased milk production of lactating rats (p < 0.05). The levels of mRNA expression of LALBA and AQPs were significantly upregulated by 105 mg/kg/day of PHF or 2.7 mg/kg of domperidone administration (p < 0.0001). Histopathological analysis of mammary glands shows that alveoli diameter was increase 14.59 and 19.33% at 105 mg/kg of PHF and 2.7 mg/kg of domperidone treatment, respectively. CONCLUSION: The study suggested that PHF has potentially to induce galactagogue activity on lactating period through upregulation of LALBA and AQP genes at the mRNA level.

Determining the association between polymorphisms of the DAT1 and DRD4 genes with attention deficit hyperactivity disorder in children from Java Island.

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurobehavioural in the children. Genetic factor is known one of the factors which contributed in ADHD development. VNTR polymorphism in 3'UTR exon 15 of DAT1 gene and exon 3 of DRD4 gene are reported to be associated in ADHD. In this study we examine the association of ADHD with VNTR polymorphism of DAT1 and DRD4 gene in Indonesian children. Sixty-five ADHD children and 70 normal children (6-13 years of age), were included in the study, we matched by age and gender. ADHD was diagnosed by DSM-IV. We performed a casecontrol study to found the association between ADHD and VNTR polymorphism of DAT1 and DRD4 genes. The 10-repeat allele of DAT1 and 2-repeat allele of DRD4 were higher in Indonesian children. Although the frequency of these allele was higher, but it was similar both in ADHD and control groups. Neither DAT1 nor DRD4 gene showed showed significant difference in genotype distribution and frequency allele between both groups (p > 0.05). No association between ADHD and VNTR polymorphism of DAT1 and DRD4 genes found in Indonesian children. This data suggest that DAT1 and DRD4 do not contribute to etiology of ADHD in Indonesian children. Further studies are needed to clarify association between VNTR polymorphism of DAT1 and DRD4 genetic with ADHD of Indonesian children in larger sample size and family based study.

Profile of Endothelin-1, Nitric Oxide, and Prostacyclin Levels in Pulmonary Arterial Hypertension Related to Uncorrected Atrial Septal Defect: Results from a Single Center Study in Indonesia.

METHODS: The study design was cross-sectional. The subjects were adult uncorrected secundum ASD with PAH. Pulmonary artery pressure was measured with right heart catheterization. Pulmonary venous blood was obtained during catheterization for measuring endothelin-1, prostacyclin, and nitric oxide. Correlation tests were performed to determine any association between biomarkers and mean pulmonary artery pressure (mPAP). The levels of biomarkers were compared based on the severity of PAH. Statistical significance was determined at p < 0.05. RESULTS: Forty-four subjects were enrolled in this study. Endothelin-1 level and mPAP had significant moderate positive correlation (r = 0.423 and p value = 0.004). However, no significant correlation was observed between prostacyclin, nitric oxide levels, and mPAP. The pattern of endothelin-1, prostacyclin, and nitric oxide was distinctive. Levels of endothelin-1 were incrementally increased from mild, moderate, to severe PAH. The levels of prostacyclin and nitric oxide had similar pattern in association with the severity of PAH, which was increased in mild-to-moderate PAH but decreased in severe PAH. CONCLUSIONS: There was a distinctive pattern of endothelin-1, prostacyclin, and nitric oxide based on severity of PAH in adult uncorrected ASD. Significant correlations existed between endothelin-1 and the severity of PAH and mPAP.

Variation of Resistin Gene Is Correlated with Insulin Resistance in Obese People of Indonesia.

BACKGROUND: Obesity is considered associated with an increase of resistin levels that plays a role in the regulation of energy and maintaining fasting blood glucose. Polymorphism of resistin is thought to be correlated with the levels of resistin and insulin resistance. AIM: This study aimed to examine the association of +299G > A and -420C > G resistin (RETN) gene with resistin level and insulin resistance in obese people of Indonesia. METHODS: We examined 142 healthy unrelated subjects consisting of 71 obese and 71 controls. Fasting blood glucose was measured by the enzymatic method while the resistin and insulin levels were measured by Elisa method. Insulin resistance was calculated by HOMA-IR index. Polymorphisms of RETN genes were examined by the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method, and the data was tested. The data were correlated with Kruskal Wallis continue logistic regression and simple linear regression. RESULTS: In the obese group, there was an increased level of insulin (17.74 vs 11.27 mU/L) and insulin resistance (HOMA-IR 3.9 vs 1.46) compared to the control group. Polymorphism of +299G > A was associated with insulin resistance (GA and GA + AA genotype significantly different compare GG genotype with P < 0.001). Resistin level was negatively correlated with insulin level (P = 0.017). CONCLUSION: In this study, polymorphism of +299G > A was identified as a risk factor for insulin resistance, and there was a significant association of serum resistin level with insulin level in the population of Indonesia.

Association between heterozygote Val92Met MC1R gene polymorphisms with incidence of melasma: a study of Javanese women population in Yogyakarta.

Introduction: Melasma is an acquired hypermelanosis of the face. The pathogenesis of melasma is multifactorial and may be caused by interactions between genetics and the environment. Research has shown that skin pigmentation is regulated by the Melanocortin-1 Receptor gene (MC1R). In Japanese populations, Val92Met and Arg163Gln genotypes of MC1R gene polymorphisms are associated with freckles and lentigo solaris, because they have skin types II-III, but for Indonesians who are skin type IV, hyperpigmentation disorders are often melasma. Purpose: This study aimed to identify the association between Val92Met and Arg163Gln genotypes of MC1R gene polymorphisms with the incidence of melasma in a Javanese women population. Patients and methods: This study used unmatched case-control design, conducted by clinical examination and questionnaire. Data were analyzed with Chi-squared test and Odds Ratio (OR). Results: This study evaluated 158 Javanese women from 18-60 years old with 79 case and 79 control subjects. The genotype of Val92Met was found more common in melasma subjects than in non-melasma (p=0.005) with (OR2.53; 95% CI:1.21-5.29). By using a bivariate test we showed sun exposure and family history of melasma were risk factors for melasma (OR:1.99; 95% CI:1.04-3.78) and (OR:35.32; 95% CI:10.25-121.70). However, genotype of Arg163Gln was not a risk factor for the incidence of melasma (OR: 0.86; 95% CI:0.39-1.89). Conclusion: The findings showed Val92Met genotypes, sun exposure and family history were risk factors for melasma incidence. This is the first study on incidence of melasma in an Indonesian population and contributes to ongoing efforts to understand the mechanisms of melasma.

Comparison of Mean VEGF-A Expression Between Acute Ischemic Stroke Patients and Non-Ischemic Stroke Subjects.

BACKGROUND: Glucose and oxygen supply to neurons are disrupted during acute ischemic stroke, resulting in hypoxia. This event, in turn, activates the transcription of hypoxia-inducible factor (HIF-1), which is responsible for activating genes responsible for angiogenesis, including vascular endothelial growth factor (VEGF). VEGF and their receptor systems exert complex mechanisms of angiogenesis, including the stimulator, inhibitors, angiogenic and modulator. VEGF-A is the primary regulator of angiogenesis, both during physiological and pathological conditions. Nevertheless, the role of VEGF on the prognosis of hypoxia remains controversial. AIM: The purpose of this study was to address if there is any difference between the mean expression of VEGF-A between acute ischemic patients and non-ischemic stroke subjects. METHODS: This was an observational study with a cross-sectional design, the population in this research is the acute ischemic stroke patients and non-ischemic stroke subjects, which were admitted on Emergency Room and later treated in the Stroke Unit, Dr Sardjito General Hospital, Yogyakarta, Indonesia. Subjects were recruited using the purposive method, yielding a total of 64 subjects on both groups. Diagnosis of acute ischemic stroke was established using a head CT scan. Patients who meet the inclusion criteria and willing to participate in the study were asked to provide informed consent. Laboratory analysis was conducted during the first 24 hours after being treated at Stroke Unit, Dr Sardjito General Hospital, Yogyakarta, Indonesia, with venous blood was withdrawn VEGF-A levels between acute ischemic stroke and non-ischemic stroke subjects were subsequently compared. Categorical variables (including gender) were tested using either chi-square or Fisher exact test. Interval data was examined using student t-test if data distribution was normal. RESULTS: As many as 35 acute ischemic stroke and 35 non-ischemic stroke patients were included in the study, among whom were 18 men (51.43%) and 17 women (48.57%) among stroke patients and 21 (60%) men and 14 (40%) women among subjects without stroke. The average of the subject's age on stroke and non-ischemic stroke group was 58.51 and 48.57 years old. VEGF-A levels were significantly higher in the non-stroke group (561.77 ± 377.92) compared with stroke group (397.78 ± 181.53) with p = 0.02. CONCLUSION: expression of VEGF-A in acute ischemic stroke group was lower when compared with the non-stroke group.

Age Stratification in Genetic Variation of Lipoprotein Lipase in Metabolic Syndrome Javanese Ethnics of Indonesia.

BACKGROUND: Metabolic syndrome (Met-S) that caused by heredity and Lipoprotein Lipase (LPL). LPL is involved in the metabolism of serum lipids. Variations in LPL alter enzyme activity, and the most common variations are LPL +495 T > G and LPL Pvu II C > T. AIM: This study aimed to identify the role of LPL +495 T > G and LPL PvuII C > T gene variations in subjects with Met-S in Javanese ethnic based on age stratification. METHODS: We recruited 160 participants of Javanese ethnicity consisting of 80 cases and 80 control subjects. Met-S was diagnosed according to the criteria of NCEP ATP III. Peripheral blood samples were collected to determine biochemical parameters. Screening for both polymorphisms was made by PCR-RFLP. RESULTS: Results found that genotype and allele frequencies for LPL +495 T > G were not significantly different between Met-S and controls with and without age stratification. In LPL PvuII C > T based on age stratification, there were significant differences between TT vs CC, recessive and dominant models in Met-S and control. In the age group > 45 years CC genotypes and TC+CC had increased risk of Met-S compared to TT genotypes. In summary, there was no significant association between LPL +495 T > G gene variation with Met-S. CONCLUSION: In LPL PvuII gene variation, TC + CC is the risk genotype of Met-S in the age group > 45 years.

Association between Increased Matrix Metalloproteinase-9 (MMP-9) Levels with Hyperglycaemia Incidence in Acute Ischemic Stroke Patients.

BACKGROUND: Hyperglycemia is common in acute stroke patients. Hyperglycemia can induce the production of reactive oxygen species, causing increased activity of matrix metalloproteinase-9 (MMP-9). AIM: This study aimed to determine an association between the increased levels of MMP-9 and the incidence of hyperglycemia in acute ischemic stroke patients. METHODS: This is a case-control study. Acute ischemic stroke patients admitted to the Stroke Unit of a reference hospital in Yogyakarta, Indonesia was divided into the hyperglycemic and non-hyperglycemic group. Demographic and clinical characteristics of each subject were recorded, and blood levels of MMP-9 were measured. Seventy-one patients were recruited, 40 subjects in the hyperglycemic group and 31 subjects in the non-hyperglycemic group. RESULTS: The median levels of blood MMP-9 level in the hyperglycemic and non-hyperglycemic group were 974.37 and 748.48 ng/mL, respectively, and the difference was statistically not significant (95% CI, 191.24-2849.53; p = 0.07). When the calculated cut-off point of 600.99 ng/mL was used, the proportion of patients with higher MMP-9 levels was significantly more in the hyperglycemic group compared with the ones in the non-hyperglycemic group (82.5% and 54.8%, respectively; OR = 3.88; p = 0.011). CONCLUSION: We concluded that the proportion of patients with MMP-9 level >600.99 ng/mL was significantly higher in acute ischemic stroke patients with hyperglycemia.

Vascular Endothelial Growth Factor 936 C/T Gene Polymorphism in Indonesian Subjects with Diabetic Polyneuropathy.

AIM: This study aimed to confirm the role of f VEGF gene 936 C/T polymorphism and Diabetic Polyneuropathy (DPN) in the Indonesian population as well as to investigate its relationship with VEGF-A level and the role of vascular risk factors. MATERIAL AND METHODS: This was a cross-sectional study involving 152 subjects. Clinical symptoms and signs of DPN were examined using DNE and DNS scoring followed by nerve conduction study. All subjects underwent anthropometric, clinical examination and laboratory procedures to obtain body mass index, HbA1C level, lipid profile, Polymorphism of +936 C/T VEGF gene (PCR-RFLP technique), and VEGF-A plasma level (ELISA). Statistical analysis using a t-test or Mann-Whitney was performed to assess continuous data and Chi-square for categorical data. Multivariate logistic regressions were also performed to determine the relationship between independent variables and DPN. RESULTS: Sixty-nine (45.4%) fulfilled the diagnostic criteria of DPN. There was a significant association between CT + TT genotype and DPN (OR 0.35 95%CI 0.16-0.79 p = 0.01). Multivariate logistic regression showed that plasma VEGF-A level (OR = 1.003; 95% CI = 1.000-1.007; p = 0.03), diabetes duration (OR = 1.108; 95% CI = 1.045-1.175; p = 0.001), and CT+TT genotype (OR = 0.347; 95%CI = 0.148-0.817; p = 0.013) were associated with DPN. Sub-group analysis on subjects with HbA1C level ≥7% showed that VEGF-A (OR = 1.011; 95%CI = (1.004-1.017; p = 0.03), diabetes duration (OR = 1.245; 95% CI = 1.117-1.388; p < 0.001), CT + TT genotype (OR = 0.259; 95%CI = 0.074-0.911p = 0.035), with an adition of HDL (OR = 0.916; 95% CI = 0.857-0.978; p = 0.009) were significant predictors of DPN while LDL (OR = 1.017; 95% CI = 1.000-1.035; p = 0.053) acted as modifying factor. CONCLUSION: It appeared that CT + TT genotype of VEGF +936 gene might act as a protecting factor for DPN while VEGF-A, diabetes duration, HDL, and LDL acted as risk factors especially on subjects with HbA1C level ≥ 7.

Genetic Polymorphism of CYP2A6 and Its Relationship with Nicotine Metabolism in Male Bataknese Smokers Suffered from Lung Cancer in Indonesia.

BACKGROUND: Cytochrome P450 2A6 (CYP2A6) is known as an enzyme which is responsible for the metabolism of chemical compounds. AIM: This study aimed to analyse the relationship between CYP2A6 gene polymorphism with nicotine metabolism rates and lung cancer incidence among smokers of Batak ethnic group in Indonesia. METHODS: This study was a case-control study involving 140 research subjects through a purposive sampling technique from three hospitals in Medan, Indonesia. An examination of nicotine metabolism rates was conducted for all subjects using the 3HC/cotinine ratio parameter with LC-MS/MS technique. The examination of the CYP2A6 gene was performed with PCR-RFLP. Data were analysed with Conditional Logistic Regression test using Epi Info 7.0 software. RESULTS: The allele frequencies of CYP2A6*1A, CYP2A6*1B, and CYP2A6*4A found were 44.3%, 48.9%, and 6.8%, respectively. The *1B allele showed the highest metabolism rate. It is found that slow metabolizer individuals were 5.49 times more likely to develop lung cancer (P = 0.01, 95%CI 1.2-24.8). CONCLUSION: Among the Bataknese smokers studied, the CYP2A6*1B allele was found to be the most common allele and showed the highest rate of nicotine metabolism. However, the results show the insignificant relationship among CYP2A6 genetic polymorphism, nicotine metabolism, and lung cancer incidence.

The Prevalence of CYP2B6 Gene Polymorphisms in Malaria-endemic Population of Timor in East Nusa Tenggara Indonesia.

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.

The Role of CYP2A6 Genetic Polymorphism in Nicotine Dependence and Tobacco Consumption among Bataknese Male Smokers.

AIM: This research aimed to analyse the relationship between CYP2A6 gene polymorphism with nicotine dependence and its relation to the number of cigarette consumption among Bataknese smokers. METHOD: This study was a cross-sectional study involving 140 research subjects in Medan, Indonesia. RESULTS: Nicotine dependence rates were found to be significantly associated with the number of cigarette consumption expressed in the Brinkman Index. CONCLUSION: The *1A wild-type alleles have a greater risk of high-very high dependence rate compared to the other variants.