METHODS: Forty-one patients with thyroid disorders from University of Malaya Medical Centre were recruited. They were categorised into four groups: multinodular goitre (MNG) (n = 18), follicular thyroid adenoma (FTA) (n = 7), papillary thyroid cancer (PTC) (n = 10), and follicular thyroid cancer (FTC) (n = 6). Serum and RBC of patients were analysed for antioxidant activities, antioxidant enzymes, and biomarkers of oxidative stress. Alterations in genes encoding the antioxidant enzymes were analysed using whole exome sequencing and PCR-DNA sequencing.
RESULTS: Patients with thyroid disorders had significantly higher serum superoxide dismutase (SOD) and catalase (CAT) activities compared to control, but had lower activities in RBC. There were no significant changes in serum glutathione peroxidase (GPx) activity. Meanwhile, GPx activity in RBC was reduced in PTC and FTC, compared to control and the respective benign groups. Antioxidant activities in serum were decreased in the thyroid disorder groups when compared to the control group. The levels of malondialdehyde (MDA) were elevated in the serum of FTA group when compared to controls, while in the RBC, only the MNG and PTC groups showed higher MDA equivalents than control. Serum reactive oxygen species (ROS) levels in PTC group of both serum and RBC were significantly higher than control group. Whole exome sequencing has resulted in identification of 49 single nucleotide polymorphisms (SNPs) in MNG and PTC patients and their genotypic and allelic frequencies were calculated. Analyses of the relationship between serum enzyme activities and the total SNPs identified in both groups revealed no correlation.
DISCUSSION: Different forms of thyroid disorders influence the levels of antioxidant status in the serum and RBC of these patients, implying varying capability of preventing oxidative stress. A more comprehensive study with a larger target population should be done in order to further evaluate the relationships between antioxidant enzymes gene polymorphisms and thyroid disorders, as well as strengthening the minor evidences provided in literatures.
METHODS: Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) was used to genotype all the aforementioned gene polymorphisms. Kaplan-Meier survival function, log-rank test and Cox regression were used to investigate the effect of gene polymorphisms on the all-cause survival of NPC.
RESULTS: NPC cases carrying T/T genotype of ITGA2 C807T have poorer all-cause survival compared to those with C/C genotypes, with an adjusted HR of 2.06 (95% CI = 1.14-3.72) in individual model. The 5-year survival rate of C/C carriers was 55% compared to those with C/T and T/T where the survival rates were 50% and 43%, respectively.
CONCLUSION: The finding from the present study showed that ITGA2 C807T polymorphism could be potentially useful as a prognostic biomarker for NPC. However, the prognostic value of ITGA2 C807T polymorphism has to be validated by well-designed further studies with larger patient numbers.
METHODS: We conducted a 1 to N case-control study involving 300 nasopharyngeal carcinoma (NPC) cases and 533 controls matched by age, gender and ethnicity to investigate the effect of hOGG1 Ser326Cys, ITGA2 C807T and XPD Lys751Gln polymorphisms on NPC risk. Linkage disequilibrium and haplotype analysis were conducted to explore the association of allele combinations with NPC risk. Restriction fragment length polymorphism (RFLP-PCR) was used for DNA genotyping.
RESULTS: No significant association was observed between hOGG1 Ser326Cys and ITGA2 C807T polymorphisms with NPC risk after adjustment for age, gender, ethnicity, cigarette smoking, alcohol and salted fish consumption. Lys/Lys genotype of XPD Lys751Gln polymorphism was associated with increased NPC risk (OR = 1.60, 95% CI = 1.06-2.43). Subjects with history of smoking (OR = 1.81, 95% CI = 1.26-2.60), and salted fish consumption before age of 10 (OR = 1.77, 95% CI = 1.30-2.42) were observed to have increased odds of NPC. The odds of developing NPC of CGC haplotype was significantly higher compared to reference AGC haplotype (OR = 2.20, 95% CI = 1.06-4.58).
CONCLUSION: The allele combination of CGC from hOGG1, ITGA2 and XPD polymorphisms was significantly associated with increased odds of NPC.
MATERIALS AND METHODS: The study included 43 obese children and 40 normal weight children. Anthropometric body measurements, bio-specimen and biochemistry assays were done. Genotyping of rs9465871 (CDKAL1) was conducted.
RESULTS: The percentages of the CC, CT, and TT genotypes of rs9465871in the lean children were 15%, 42.5%, and 42.5%, respectively. Regarding obese children, the frequencies were 18.6%, 58.1% and 23.3% respectively with no significant statistical difference. Comparison between the CDKAL1 rs 9465871 polymorphism showed that the highest value of fasting insulin was recorded in CC genotype (22.80± 15.18 [uIU/mL] P
METHODS: A total of 1114 subjects comprising of 536 PD patients and 578 healthy controls of Malay ancestry were recruited and genotyped using Taqman® allelic discrimination assays.
RESULTS: The G allele of rs10513789 (OR = 0.83, p = 0.001) and A allele of rs12637471 (OR = 0.79, p = 0.007) in the MCCC1/LAMP3 locus were associated with a protective effect against developing PD in the Malay population. A recessive model of penetrance showed a protective effect of the GG genotype for rs10513789 and the AA genotype for rs12637471. No association with PD was found with the other MCCC1/LAMP3 rs12493050 variant or with the DGKQ (rs11248060) variant. No significant associations were found between the four variants with the age at PD diagnosis.
CONCLUSION: MCCC1/LAMP3 variants rs10513789 and rs12637471 protect against PD in the Malay population.