Lack of methylation changes in GJB2 and RB1 non-coding regions of cochlear implant patients with sensorineural hearing loss

Objective@#Recent advances in epigenetic studies continue to reveal novel mechanisms of gene regulation and control, however little is known on the role of epigenetics in sensorineural hearing loss (SNHL) in humans. We aimed to investigate the methylation patterns of two regions, one in RB1 and another in GJB2 in Filipino patients with SNHL compared to hearing control individuals. @*Methods@#We investigated an RB1 promoter region that was previously identified as differentially methylated in children with SNHL and lead exposure. Additionally, we investigated a sequence in an enhancer-like region within GJB2 that contains four CpGs in close proximity. Bisulfite conversion was performed on salivary DNA samples from 15 children with SNHL and 45 unrelated ethnically-matched individuals. We then performed methylation-specific real-time PCR analysis (qMSP) using TaqMan® probes to determine percentage methylation of the two regions. @*Results@#Using qMSP, both our cases and controls had zero methylation at the targeted GJB2 and RB1 regions. @*Conclusion@#Our study showed no changes in methylation at the selected CpG regions in RB1 and GJB2 in the two comparison groups with or without SNHL. This may be due to a lack of environmental exposures to these target regions. Other epigenetic marks may be present around these regions as well as those of other HL-associated genes.

Genetic polymorphisms in NAT1, NAT2, GSTM1, GSTP1 and GSTT1 and susceptibility to colorectal cancer among Filipinos

@#Objectives. Polymorphisms in metabolic genes which alter rates of bioactivation and detoxification have been shown to modulate susceptibility to colorectal cancer. This study sought to evaluate the colorectal cancer risk from environmental factors and to do polymorphism studies on genes that code for Phase I and II xenobiotic metabolic enzymes among Filipino colorectal cancer patients and matched controls. Methods. A total of 224 colorectal cancer cases and 276 controls from the Filipino population were genotyped for selected polymorphisms in GSTM1, GSTP1, GSTT1, NAT1 and NAT2. Medical and diet histories, occupational exposure and demographic data were also collected for all subject participants.Results. Univariate logistic regression of non-genetic factors identified exposure to UV (sunlight) (OR 1.99, 95% CI: 1.16-3.39) and wood dust (OR 2.66, 95% CI: 1.21-5.83) and moldy food exposure (OR 1.61, 95% CI:1.11-2.35) as risk factors; while the NAT2*6B allele (recessive model OR 1.51, 95% CI :1.06-2.16; dominant model OR 1.87, 95% CI: 1.05-3.33) and homozygous genotype (OR 2.19, 95% CI: 1.19-4.03) were found to be significant among the genetic factors. After multivariate logistic regression of both environmental and genetic factors, only UV radiation exposure (OR 2.08, 95% CI: 1.21-3.58) and wood dust exposure (OR 2.08, 95% CI: 0.95-5.30) remained to be significantly associated with increasing colorectal cancer risk in the study population.Conclusion. This study demonstrated that UV sunlight and wood dust exposure play a greater role in influencing colorectal cancer susceptibility than genotype status from genetic polymorphisms of the GST and the NAT` genes.

The Philippine National Ear Institute: Patient and audilogic profiles

Background: The Philippine National Ear Institute (PNEI) was created to promote health of hearing and balance among Filipinos. Over the years, it has provided audiologic services to thousands of patients annually and has published relevant hearing and balance research. Objective: To describe the patients served by the PNEI in terms of age, region of origin, occupation, pretest diagnosis, and audiologic results. Methods: Study Design - Cross-sectional study Setting - National tertiary care center Population - All records of patients referred for audiologic testing at PNEI in 2006 were reviewed and encoded into analyzable format. Results: A total of 1,756 patients had audiologic records for review. Median age was 32.5 years, with the age distribution presented according to sex, type of tests done including common reasons for referral, and median threshold levels by frequency. Coverage was national in scope, with most patients coming from the National Capital Region and from Regions III and IVa. Occupation was indicated in 37.8 percent of the working age group, most of whom were unemployed. The most common pretest diagnosis was chronic otitis media (26.6 percent), followed by hearing loss of unknown etiology (13.0 percent) and tinnitus (9.3 percent). Severity of hearing impairment based on pure tone audiometry was variable, and was presented according to common diagnoses. About 39 percent of hearing impairment cases were sensorineural, 36 percent conductive and 25 percent due to mixed defect. Bilateral Type A ears were found in 45.4 percent of patients by tympanometry, while 29.3 percent were bilateral Type B. For otoacoustic emissions, 69.0 percent were labeled as "refer" in at least one ear. Conclusion: The PNEI is a major national referral center for audiology that holds much promise in developing programs for national surveillance of the hearing status of different sectors in Philippine society. (Author)