BACKGROUND AND OBJECTIVE

Choledochal cysts (CC) are rare congenital, cystic dilations of the biliary tree occurring predominantly in Asian populations and in females. Patients are usually children presenting with any of the following: abdominal pain, palpable abdominal mass, and jaundice. Its congenital nature hints at a potential genetic cause. A possible causal gene is TP53, a tumor suppressor with a germline variant called rs201753350 (c.91G>A) that changed from a G allele to an A allele, decreasing the cell proliferation suppressing activity of its functional protein. Currently, there is no information on the TP53 rs201753350 germline variant available for the Filipino population. This study determined the prevalence of rs201753350 and the association between the functional G allele, the rs201753350 germline variant A allele, and the occurrence of CCs in Filipino pediatric patients in a tertiary government hospital.

Genomic DNA was extracted from blood samples of pediatric patients clinically diagnosed with CC. Controls were DNA samples collected from a previous study. The samples underwent PCR, electrophoresis, and sequencing.

A total of 109 participants (22 cases and 87 controls) were included in the study. The A allele (22.94%) occurs at a lower frequency than the G allele (77.06%) among both cases and controls. More individuals have a homozygous G/G genotype (54.13%) than a heterozygous A/G genotype (45.87%) while the homozygous A/A genotype was not observed. The estimated risk of choledochal cyst occurrence is significantly lower in individuals with the A allele (PR: 0.08, 95% CI: 0.01 – 0.55) and the A/G genotype (PR: 0.06, 95% CI: 0.01 – 0.40).

There is no significant evidence to suggest an association between the TP53 rs201753350 germline variant and the occurrence of choledochal cysts in Filipinos. It is recommended that other mutations within and beyond the TP53 gene be investigated for possible associations with choledochal cyst occurrence.

Background and Objective. Choledochal cysts (CC) are rare congenital, cystic dilations of the biliary tree occurring predominantly in Asian populations and in females. Patients are usually children presenting with any of the following: abdominal pain, palpable abdominal mass, and jaundice. Its congenital nature hints at a potential genetic cause. A possible causal gene is TP53, a tumor suppressor with a germline variant called rs201753350 (c.91G>A) that changed from a G allele to an A allele, decreasing the cell proliferation suppressing activity of its functional protein. Currently, there is no information on the TP53 rs201753350 germline variant available for the Filipino population. This study determined the prevalence of rs201753350 and the association between the functional G allele, the rs201753350 germline variant A allele, and the occurrence of CCs in Filipino pediatric patients in a tertiary government hospital. Methods. Genomic DNA was extracted from blood samples of pediatric patients clinically diagnosed with CC. Controls were DNA samples collected from a previous study. The samples underwent PCR, electrophoresis, and sequencing. Results. A total of 109 participants (22 cases and 87 controls) were included in the study. The A allele (22.94%) occurs at a lower frequency than the G allele (77.06%) among both cases and controls. More individuals have a homozygous G/G genotype (54.13%) than a heterozygous A/G genotype (45.87%) while the homozygous A/A genotype was not observed. The estimated risk of choledochal cyst occurrence is significantly lower in individuals with the A allele (PR: 0.08, 95% CI: 0.01 – 0.55) and the A/G genotype (PR: 0.06, 95% CI: 0.01 – 0.40). Conclusion. There is no significant evidence to suggest an association between the TP53 rs201753350 germline variant and the occurrence of choledochal cysts in Filipinos. It is recommended that other mutations within and beyond the TP53 gene be investigated for possible associations with choledochal cyst occurrence.
Jaundice

The Philippines has an increasingly aging population thereby increasing the demand for healthcare and support from families. Studies showed that the family is the main caregiver of elderly parents/adults as dictated by the Filipino culture of filial piety and respectful behavior towards older people. However, this caring culture is now slowly declining, and Filipino older adults also experience abuse, exploitation, and other forms of neglect from their families. This special article described that the declining caring culture was due to deteriorating family values and societal influences brought about by modernization. This paper also highlights the crucial role of the family and the community in inculcating the preservation of this valued caring Filipino culture, especially among the youth. In cases where senior citizens are being abused and neglected by their families, the state steps in to safeguard the welfare and protection of Filipino senior citizens. Enacted and promulgated laws ensure social justice and protection of human dignity among Filipino older adults as well as the provision of socioeconomic and health needs. In conclusion, the preservation of a caring culture through educating the youth coupled with the implementation of enacted and promulgated laws of the country ensures the quality of aging life among Filipino older adults.

The Philippines is a densely populated nation faced with multiple challenges in the healthcare field given its geographic, cultural, and socioeconomic barriers. Due to the geographic limitations of medical services in the country, many patients must travel a great distance to referral centers. This was further exacerbated by the Coronavirus disease 2019 (COVID-19) pandemic, which spread across the world and upended lives. This pandemic triggered a public health crisis that impacted healthcare systems, healthcare workers, and communities worldwide. It compounded current difficulties with the provision and accessibility of medical services, necessitating the employment of alternative methods of providing health coverage. As a result, advanced technological methods for patient diagnosis, monitoring, treatment, and counseling were rapidly implemented.1 Interest in these technological advances began prior to the COVID-19 pandemic, though primarily in developed countries. However, during this global outbreak, telehealth practices – which refer to online health care services provided by all health care professions – have seen a rapid increase in popularity.2,3 Telehealth was brought to the forefront in all countries in order to surmount lockdown constraints, allow continuous provision of health care for patients, and limit exposure to health systems and health providers.4 Traditional medical education and training were likewise disrupted during this time, resulting in the incorporation of telehealth into medical education. To reduce the risks associated with more personnel in the hospital, medical students were withdrawn from clinical environments during the COVID-19 outbreak. This created an environment of uncertainty and limited clinical exposure, with concerns surrounding progression through the medical course and training program.5 Continuing medical education, which has traditionally been based on clinical knowledge and skills, now requires online technical communication skills. Innovative services were rapidly developed with health professionals embracing this new technological competence, enabling general consultation for patients, remote patient monitoring, and self-directed patient care, thereby decreasing the burden on health facilities. Digital learning platforms also provided an effective way to address the learning gaps caused by the pandemic. The restriction of “in-person” delivery of healthcare services due to the global outbreak has prompted physicians, including clinical geneticists and genetic counselors, to investigate alternative methods of providing health care to patients. A telehealth innovation for online delivery of clinical genetic and genetic counseling services is the Philippine General Hospital’s Telegenetics Service. Despite being launched in 2013 to serve genetics patients across the country, this service has since been upgraded and capitalized resulting in patient appreciation for its COVID-19 exposure prevention, increased access, and time and cost efficiency. However, the telegenetics service has its limitations.6,7 Despite the expanding scope of telehealth/telegenetics and its immediate application, issues such as data/patient privacy, organizational readiness, digital maturity, regulatory impediments, access and acceptance of the technology, geographical and digital disparities, and its integration with traditional medical services have emerged.8 Lack of a detailed physical examination is also lost in a virtual visit, with focused questions leading to fragmented, impersonal interactions. Even when restrictions were lifted, telehealth usage nonetheless remained significantly higher than it had been prior to the pandemic. This may indicate a shift in public opinion in favor of this innovative medical practice.9 With the expansion of genetic services in the country, there is now a greater need for telegenetics due to the increased demand for clinical genetic and genetic counseling expertise. Therefore, evidence on the safety and efficacy of this technology in comparison to the traditional healthcare delivery approach is required. If the technology has the potential to improve health care, we must guarantee its availability in all resource-limited areas. Future efforts should thus focus on establishing solutions to address the aforementioned issues and concerns within our healthcare and education systems, thereby ultimately enhancing the standard of medical care.
Philippines ; health care ; COVID-19

Introduction: Thalassemias and hemoglobinopathies are autosomal-recessive red blood cell disorders affecting hemoglobin (Hb) quantity and/or quality. Clinical manifestations vary from clinically asymptomatic to transfusion dependent individuals. These disorders are global in scope and is prevalent in Southeast Asia hence screening in the Philippines is very crucial for its prevention and control. Objective: Our retrospective study aimed to determine the frequency of thalassemias and hemoglobinopathies in patients referred to the Molecular Genetics Unit, Institute of Human Genetics, National Institutes of Health, University of the Philippines, Manila for High Performance Liquid Chromatography (HPLC) screening. Methods: Blood samples from patients (n=622) sent by hematologists from different parts of the country from October 2008 to February 2015 were analyzed. Extracted whole blood samples from the subjects were anticoagulated with ethylenediaminetetraacetic acid (EDTA) and were analyzed using BIORAD VARIANT™ HPLC Testing System and VARIANT™ Beta Thalassemia Short (BTS) Program kit for the detection of abnormalities in hemoglobin. Interpretation of results were based on the submitted mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) values, and Hb typing via HPLC of the patients. Results: Approximately twenty-nine percent (29.10%, n=181) of subjects were presumptively identified with thalassemias and hemoglobinopathies by HPLC. Beta-thalassemia trait, Hb E trait, and beta-thalassemia/Hb E disease were detected in 65 (10.45 %), 14 (2.25 %), and 3 (0.48 %) subjects, respectively. While suspected alpha-thalassemia, presumably Hb H disease, was found in 99 (15.92 %) patients. Interestingly, seventy-two percent (72.11%, n=318) of the patients with normal Hb typing via HPLC have low MCV and MCH values. Conclusion Results of this study provide the spectrum and frequency of thalassemias and hemoglobinopathies in patients referred to our laboratory for HPLC analysis.
Thalassemia ; Hemoglobinopathies ; Chromatography, High Pressure Liquid ; Erythrocyte Indices

Introduction: Midwives play an important role in promoting newborn screening (NBS) and they ensure that all Filipino newborns are offered screening for life-threatening metabolic conditions. Of the disorders included in NBS, Glucose 6 Phosphate Dehydrogenase (G6PD) deficiency is the most common disorder detected. Objectives: This study aimed to assess the knowledge, self-perceived role, and experience of midwives who practice in urban and rural settings in educating parents of a newborn who are confirmed cases for G6PD deficiency. Method: One-on-one semi structured interview was conducted among 21 midwives from Manila City and Lipa, Batangas, Philippines. Results: The study findings indicate that midwives frequently serve as the primary information resource for parents of infants with G6PD deficiency. Assessment of knowledge showed that midwives have sufficient knowledge about the medical management and the necessary follow-up of infants with G6PD deficiency. However, it also revealed that they have inadequate knowledge of the underlying genetic cause of G6PD deficiency. The surveyed midwives recognized their role and the importance of proper education regarding G6PD deficiency. Conclusion The findings of this study identified gaps in the midwives’ knowledge on the genetic mechanisms and inheritance of G6PD deficiency, which could be a basis to improve the education and dissemination of information and to eventually improve parental education and care of newborns with G6PD deficiency
Genetic Counseling ; Glucosephosphate Dehydrogenase Deficiency ; Neonatal Screening

Objective: The observed irregularities in the biochemical profile and the limited information on long-term outcomes among patients with Duarte variant (D/G) galactosemia have led to patient management variability. This study examined the molecular characteristics of Filipino patients with presumed variant galactosemia for confirmation of diagnosis. It also aimed to describe the corresponding biochemical, clinical and neurodevelopmental profiles in order to gain a better understanding of the patients with normal galactose metabolites in spite of low to absent GALT activity detected by the local newborn screening program. Methods: Thirteen (13) patients who were presumed to have a variant form of galactosemia by national newborn screening between 2002 and 2010, and who previously underwent physical and neurodevelopmental assessment were included in the study. Repeat clinical, ophthalmologic and neurodevelopmental evaluations were done upon recruitment of participants. Direct sequence analysis of the coding region of the GALT gene was conducted to determine the patients’ genotypes. Results: None of the patients’ genotypes were consistent with Duarte variant (D/G) galactosemia. Their genotypes reflect the normal total blood galactose levels in patients, but were inconsistent with the absent or trace GALT activity. Conclusion Molecular testing for the entire cohort of presumed “variant” galactosemia Filipino patients will provide better profiling of this condition. Re-evaluation and assessment of the current guidelines used by national newborn screening in classifying variant galactosemia are recommended.
Galactosemias ; Neonatal Screening

Background: Extrahepatic biliary atresia (EHBA) causes a rare obstructive cholestasis in infants. Kasai portoenterostomy if done before the third month of life may relieve obstruction. Genetic predisposition has been implicated in EHBA etiopathogenesis with rs17095355 polymorphism having the strongest association. We determined the association between rs17095355 and EHBA susceptibility of Filipino children, and described the outcome in each genotype among timely operated patients. Methods: Thirty-four histologically diagnosed EHBA patients and thirty-three age- and sex-matched controls were recruited. Genomic DNA was extracted from peripheral blood and subjected to PCR and direct sequencing. Success of surgery among patients operated before 90 days of life was assessed by jaundice clearance six months post-surgery and native liver survival two and five years post-surgery. Results: There was no significant difference among individuals carrying T and C alleles in developing EHBA (OR:1.36; 95%CI:0.65–2.86). Jaundice persisted post-operatively in 75%, 33% and 27% of Kasai-operated homozygous T (T/T), homozygous C (C/C) and heterozygous (C/T) patients, respectively. Fifty percent of Kasai-operated C/C and C/T patients retained their native liver whereas all Kasai-operated T/T patients required liver transplantation two years post-surgery. Conclusion There is insufficient evidence to associate rs17095355 in EHBA development among Filipinos. Further investigation is warranted to elucidate genetic mechanisms in EHBA etiopathogenesis.
Biliary Atresia ; Polymorphism, Single Nucleotide ; Portoenterostomy, Hepatic

Objectives: The highly polymorphic nature of the CYP2D6 gene and its central role in the metabolism of commonly used drugs make it an ideal candidate for pharmacogenetic screening. This study aims to determine the prevalence of CYP2D6 polymorphisms among Filipinos and their association to lung cancer. Method: Forty seven single nucleotide polymorphisms (SNPs) of the CYP2D6 gene were genotyped from DNA samples of 115 cases with lung cancer and age- and sex-matched 115 controls. Results: Results show that 18 out of 47 polymorphisms have significant genotypic variability (>1% for at least 2 genotypes). No variant is associated with lung cancer. However, rs1135840, rs16947 and rs28360521, were found to be highly variable among Filipinos. Conclusion This study demonstrated that CYP2D6 polymorphisms are present among Filipinos, which, although not found to be associated with lung cancer, can be useful biomarkers for future pharmacogenetic studies. The SNP rs16947 is found to be associated with cancer and timolol-induced bradycardia; the SNP rs1135840, on the other hand, is only shown to be linked with cancer. The genetic variant rs28360521 is known to be associated with low-dose aspirin-induced lower gastrointestinal bleeding.
Pharmacogenetics ; Cytochrome P-450 CYP2D6 ; Lung Neoplasms ; Biomarkers

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.
Colorectal Neoplasms ; Polymorphism, Genetic