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.

Association of -308G/A TNF- alpha gene polymorphism and spontaneous preterm birth in acehnese ethnic group, Indonesia: this polymorphism is not associated with preterm birth

Background: Single nucleotide polymorphism [SNP] within tumor necrosis factor alpha [TNF-alpha] gene promoter [-308G/A TNFA] is associated with higher gene expression. The role of this SNP as a risk factor for spontaneous preterm birth has been assessed in some regions and the findings were significantly different between race and ethnic groups

Aim: To provide the scientific evidence whether allele A within SNP -308G/A TNFA promoter is a risk factor for spontaneous preterm birth among Acehnese ethnic or not

Subjects and methods: In this case-control study, the genotypes of SNP -308G/A TNFA among 40 patients with spontaneous preterm birth and 40 patients with term birth were determined by real-time polymerase chain reaction [RT-PCR]. The concentrations of TNF-alpha from blood were measured by enzyme-linked immunosorbent assay [ELISA]. The differences in genotype distributions, dominant and recessive models, and allele frequencies between case and control groups were analyzed with Chi-squared test. Deviation of genotype frequencies from the Hardy-Weinberg equilibrium [HWE] was assessed by Fisher's exact test

Results: This study found that the concentration of TNF-alpha between preterm and control groups was not statistically different, 5.5 +/- 2.9 mg/dL vs. 10.1 +/- 17.9 mg/dL, p = 0.112. The level of TNF-alpha had no strong association with either genotype distribution or allele frequency of SNP -308G/A TNFA. Furthermore, there was no association between mutant genotypes and spontaneous preterm birth [OR: 0.32; 95%CI: 0.08-1.33, p = 0.096] and between mutant allele and spontaneous preterm birth [OR: 0.35; 95%CI: 0.09-1.37, p = 0.105]

Conclusion: SNP -308G/A TNFA is not associated with spontaneous preterm birth in Acehnese ethnic group

promoter region [G-800A and C-509T] polymorphisms of transforming growth factor-01 gene among young women with recurrent urinary tract infection

Recurrent urinary tract infection [UTI] is common among young women and one of its risk factors is genetic. Polymorphisms in promoter region [G-800A [rs 1800468] and C-509T [rsl800469]] of transforming growth factor-[beta1 [TGF-beta1] gene play pivotal roles in several infection diseases but the association of these polymorphisms with recurrent UTI remains unclear. The aim of this study was to assess the correlation of TGF-beta1 G-800A and C-509T polymorphisms with recurrent UTI in young women. TGF-beta1 G-800A and C-509T polymorphisms among 34 recurrent UTI patients and 34 healthy subjects, aged 15-50 years old, were evaluated with polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] and confirmed by DNA sequencing. At position -800, genotypes showed no significant differences between recurrent UTI patients [GG 97.1%; GA 2.9%; AA 0%] and normal control [GG 97%; GA 0%; AA 2.9%] young women. Dominant and recessive model analyses did not find significant correlation between recurrent UTI patients and normal control young women. At position -509, allelic and genotypic frequencies showed no significant differences between recurrent UTI patients [CC 20.6%; CT 61.8%; TT 17.7%] and control individuals [CC 2.9%; CT 73.6%; TT 23.5%]. This study found that there is no strong correlation between polymorphisms of TGF-beta1 G-800A and C-509T and recurrent UTI