RESUMO
Genome-wide association studies have shown that a non-synonymous single nucleotide polymorphism characterized by a C-to-G change encoding an isoleucine-to-methionine substitution at amino acid position 148 in the human patatin-like phospholipase 3 (PNPLA3) gene was found to be associated with non-alcoholic fatty liver disease (NAFLD) and advanced liver damage. A hospital-based study was conducted to determine the distribution of PNPLA3 genotypes among patients clinically diagnosed and histologically confirmed with NAFLD and among normal controls. We also compared the allelic frequencies of PNPLA3 with different ethnic populations. More importantly, we evaluated the association between PNPLA3 genetic variation and risk of developing NAFLD among Filipinos. Real-time PCR was performed using the Taqman SNP genotyping assay for rs738409. Nucleotide sequencing was performed to confirm the PNPLA3 genotypes. Allelic frequencies among normal controls were 0.83 and 0.17 for the PNPLA3 C and PNPLA3 G alleles, respectively. Calculated frequencies in Hardy Weinberg Equilibrium were 72% for PNPLA3 C/C, 22% for PNPLA3 C/G, and 6% for PNPLA3 G/G genotype. There is a significant difference in the distribution of PNPLA3 genotypes between normal controls and NAFLD patients (p = 0.0172). However, there was no significant association found between PNPLA3 genotypes and risk of developing NAFLD after controlling for possible confounding effects (p = 0.0574). Allelic frequencies of PNPLA3 among Filipinos were statistically different from Hispanics, Japanese, and Han Chinese. In conclusion, genetic variation in PNPLA3 rs738409 C>G seems to be associated with NAFLD among Filipinos. Further studies are needed to replicate our observations in an independent larger population.
RESUMO
A hospital-based cross-sectional study was conducted to determine the allelic and genotype frequencies in the genes encoding for catechol-O-methyltransferase and CYP2D6*10 among healthy volunteers and patients clinically diagnosed with cancer pain. PCR-RFLP was used to identify COMT and CYP2D6*10 genotypes. Allelic frequencies among healthy volunteer Filipinos were 0.83 and 0.17 for the COMT Val and COMT Met alleles, respectively. Calculated frequencies in Hardy-Weinberg equilibrium (HWE) were 73% for COMT Val/Val, 26% for COMT Val/Met, and 1% for COMT Met/Met genotype. For CYP2D6*10, allelic frequencies in HWE among volunteers were 0.46 for the C allele and 0.54 for the T allele. Twenty percent were identified as homozygous for the wild-type C/C genotype, 56% were identified as heterozygous for the C/T genotype, and 24% were identified as homozygous for the T/T variant genotype. No significant differences in COMT and CYP2D6*10 allele frequencies between cancer patients and healthy volunteers were noted. Our data demonstrated that the allele frequencies of COMT and CYP2D6*10 in the Filipino healthy volunteers were similar with other Asians but markedly different from Caucasian populations.
RESUMO
The glutathione S-transferase (GST) supergene family is made up of four gene families responsible for the biotransformation of drugs and other xenobiotics. Genetic variations in this supergene family influence individual detoxification levels and may contribute to the development of cancer. A hospital-based case-control study was conducted to evaluate the association between GST polymorphism among Filipino patients positive for hepatitis B virus (HBV DNA) and clinically diagnosed as either with chronic active hepatitis, liver cirrhosis, and hepatocellular carcinoma as well as normal individuals negative for HBV infection. Multiplex PCR was used to detect the presence or absence of the GSTT1 and GSTM1 polymorphisms in peripheral blood. DNA sequencing of the S gene region of the virus was used to determine the predominant genotype found among HBV-infected patients. Our results showed that the odds of having a chronic liver disease is only 0.95 (95% CI 0.58-1.57) among those with GSTT1 null genotype compared to those with GSTT1+ genotype. On the other hand, the odds of chronic liver disease is 17.85 times (95% CI 7.34-43.45) for those with GSTM1 null genotype compared to those with GSTM1+ genotype. Using the GSTT1+/GSTM1+ genotype as the reference, both GSTT1+/GSTM1- (OR 16.61; 95% CI 6.69-41.22) and GSTT1-/GSTM1- (OR 11.91; 95% CI 4.48-31.66) genotypes seem to be risk factors for chronic liver disease. From our observations, we conclude that polymorphism in GSTM1 null genotype (OR 17.85; 95% CI 7.34-43.45) seem to be associated with an increased risk of chronic liver disease among Filipinos.
