Genetic polymorphisms in CYP1A1, GSTM1, GSTP1, GSTT1, NAT1 and NAT2 and oral cavity cancer risk among Filipinos

Polymorphisms in metabolic genes have been shown to modulate susceptibility to oral cavity cancer. Cases (n=176) and controls (n=317) from the Filipino population were genotyped for selected polymorphisms in CYP1A1, GSTM1, GSTP1, GSTT1, NAT1 and NAT2. Medical and diet histories, occupational exposure and demographic data were also collected for all subjects. The CYP1A1m1/m1 genotype is protective against oral cancer, while being homozygous for the GSTP1 c.313G genotype and heterozygous for the NAT1*10 homozygotes and non-homozygotes for the CYP1A1 m1 allele. The risk from heterozygosity for the NAT1*10 allele was limited to subjects who were not homozygous for the GSTP1 c.313G genotype remained a significant oral cancer risk modifier, together with environmental variables, the homozygous GSTP1 c.313G genotype remained a significant oral cancer risk modifier, together with environmental risk factors, such as smoking, passive smoking, inverted smoking and tobacco chewing, and environmental protective factors, i.e. moderate consumption of fish sauce (patis) and shrimp paste (bagoong). The GSTP1 c.313G polymorphism increases susceptibility for oral cavity cancer in the Filipino population.

Angiotensin I-converting enzyme gene polymorphism and diabetic nephropathy in Filipino type 2 diabetes mellitus patients / Journal of the ASEAN Federation of Endocrine Societies

Objective. Previous studies have demonstrated the role of genetic susceptibility in the pathogenesis of diabetic nephropathy. The study aimed to determine the frequencies of angiotensin I-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in a pilot population of Filipino type 2 diabetic patients and normal controls. Methods. An analysis of the ACE gene polymorphism was performed in 42 diabetic patients with and without nephropathy, and 24 normal controls. The analysis was done using polymerase chain reaction, restriction enzyme digestion, and gel electrophoresis techniques to determine the polymorphism (II, DD or ID). Independent T-tests and chi-square tests were used to compare clinical characteristics, and logistic regression analysis was done to determine odds ratio for development of nephropathy. Results. The ID polymorphism of the ACE gene was more frequent (52.4%) in patients with diabetic nephropathy (n=21). In those without nephropathy (n=21), II was more common (61.9%). ID was the more frequent genotype in the normal controls (n=24) (58.3%). The odds of developing diabetic nephropathy were increased by 4.8 times in those with ID polymorphism, and 2.9 times in those with DD. Conclusion. The D allele was more common in patients with diabetic nephropathy, similar to the observation in South Indian patients. Since the study involved only a small pilot group, studies on a larger population is needed to establish the hypothesized role of the D allele in susceptibility to diabetic nephropathy in Filipinos.

Characterization of mutations and polymorphisms in the G6PD among Filipino newborns with glucose-6-phosphate dehydrogenase deficiency

Background. Glucose-6-phosphate (G6PD) deficiency is the most prevalent enzyme deficiency to date. The global prevalence of G6PD deficiency is estimated at around 330 million people affected with the disease worldwide. This 4.9 percent prevalence, correlates highly with geographic areas endemic to malaria. It is the most common among the disorders in the Newborn Screening (NBS) panel in the Philippines, with one confirmed case for every 52 newborns (1:52). This paper determines the molecular background of G6PD deficiency among Filipino newborns detected by newborn screening. Methods. A total of 200 cases confirmed to have G6PD deficiency, 180 males and 20 females, were identified through the Philippine Newborn Screening Program from 2001-2003. Genomic DNA was extracted from dried blood spots followed by multiplex polymerase chain reaction using multiple tandem forward primers and a common reverse primer (MPTP) to detect previously reported common mutations and polymorphisms in exons 5, 6, 9, 11 and 12 of the G6PD gene. Results. Of the 200 samples analyzed, mutations and polymorphisms in the G6PD gene were identified in 148 cases (74%). The most common mutation was a G to A transition on nucleotide 871 (Viangchan) of exon 9 in combination with a silent mutation on exon 11, accounting for 32.9% of the cases. This was followed by a C to T transition on nucleotide 1360 (Union) in 21.1 % of the cases. Other mutations were Vanua Lava in 10%, Chatham in 9.4% and Canton in 3.5% of the newborns. The silent polymorphism on nucleotide 1311 was present in 12.9% of cases. There were combinations of these mutations and polymorphisms present in a minority of cases. Conclusion. Results of this study showed the molecular heterogeneity underlying G6PD deficiency among Filipino newborns.

A clinical and molecular cytogenetic study of Filipino patients with williams syndrome

Objective. To study the clinical spectrum of Filipino patients with Williams Syndrome and to confirm the gene deletion by FISH analysis. Methods. From June 2005 to September 2008, patients who were seen at the Genetics clinic of the UP-PGH and who met the clinical criteria for Williams Syndrome were analyzed for the 7q11.23 deletion through karyotyping and FISH studies. A detailed history and a thorough dysmorphologic examination were performed. Relevant investigations included two-dimensional echocardiography, renal ultrasonography, ophthalmologic examination, developmental assessment and serum calcium determination. Result. Eight patients were included in the study. The mean age at first diagnosis was 8.5 years. All cases were sporadic. The chromosomal analysis was normal for all patients and in the FISH analysis, a 7q11.23 deletion was detected in 100% of cases. Distinctive facial features, cardiac abnormalities and developmental delay were present in all patients. The typical behavior of overfriendliness was observed in the majority of cases. Hypercalcemia was documented in only one case and no renal anomalies were detected. Conclusion. The craniofacial features were similar among patients but there is a broad spectrum of severity of clinical features in cardiovascular abnormalities, personality, behavior traits and mental capacity.

Intravenous pamidronate treatment in Filipino children with moderate to severe osteogenesis imperfecta

Objective. To present preliminary data on the effects of intravenous pamidronate in children with moderate to severe Osteogenesis Imperfecta (OI). Methods. This is a restrospective study wherein a review of medical records and available serial radiographs of children (N=14) with moderate to severe IO started on pamidronate from 2006 to 2010 was done. Results. Two children have IO Type I, 8 have IO Type III and 4 have IO Type IV. At baseline, 2 had normal height, 8 had height less than minus 2SD and the rest with less than minus 1SD. Twelve out of 14 had vertebral compression fractures. Mean age at start of pamidronate was 5.4 years (range 0.5-11 years). First infusion fever in five patients and transient generalized macular rash in one child were noted. Serum calcium and phosphorus levels were normal at baseline and remained stable. Based on parental report, improvement of motor function was noted. In the 10 children who had at least a year of treatment, long bone fractures decreased from mean annualized fracture rate of 2.6 at baseline to 0.9. In patients with vertebral compression fractures, serial radiographs showed improvement of vertebral shape. Conclusion. This preliminary study shows that treatment was generally well tolerated and led to decrease in long bone fractures, improved vertebral shape and improved function.

Occurrence of birth defects at the Philippine General Hospital: 2001-2010

Introduction. Birth defects are global problem with impact particularly severe in middle - to low -income countries. In the Philippines, there is a limited data on birth defects despite the fact that congenital anomalies have been in the top 10 causes of infant mortality. The objectives of the study were: 1.) to determine the occurrence of birth defects among patients admitted to the Philippine General Hospital (PGH); 2.) To present the distribution of patients by geographic location and age group distribution; 3.) To categorize birth defects by organ systems; and 4.) To categorize birth defects as either isolated, part of a recognizable syndrome, chromosomal syndrome of multi-malformed case. Methods. Patients admitted to PGH from 2001-2010 and to have major structural defects were included in this study. Case ascertainment was done through a review of medical records of all admitted patients age 0 to more than 65 years old. Patients with birth defects was assigned codes of International Classification of Diseases (ICD)-10 classification. Results. Of the 438,944 admissions to the PGH from 2001 to 2010, there were 8,686 (2.0%) patients with a diagnosis of at least one (1) birth defect. The most common birth defects are as follows: digestive system (3,605/8,686 or 41.5%), cardiovascular system (,839/8,686 or 32.7%), nervous system (1,070/8,686 or .3%) and genital organ anomalies (755/8,686 or 8.7%). The common digestive system anomalies were cleft lip and /or palate (1,548/8,686 or 17.8%), imperforate anus (698/8,686 or 8%) and hirschsprung disease (582/8,686 or 6.7%). Most of the cardiovascular system anomalies were congenital malformations of the cardiac septa (1,160/8,686 or 13.4%) and the great arteries (769/8,686 or 8.9%), while almost of the nervous system anomalies were due to congenital hydrocephalus (347/8,686 or 4%), encephalocoele (303/8,686 or 3.5%) and spina bifida (193/8,686 or 2.%) The most common genital organ anomalies were hypospadias (340/8,686 or 3.9%) and undescended testicle (233/8,686 or 2.7%) Majority (4,042/8,686 or 46.5%) of birth defect cases came from the National Capital Region (NCR) while 32.5% (or 2,87/8.686) of the cases came from region IV-A or Cavite, Laguna, Batangas , Rizal and Quezon (CALABARZON) Region. Conclusion. The results of this study show that the most common birth defects are digestive, cardiovascular, nervous system, and genital organ anomalies. This trend is similar to those reported internationally. The findings of the study can be the basis of policies toward the development and implementation of practical strategies for primary and secondary prevention of birth defects among Filipinos.

A master of science in genetic counseling program in the Philippines

In the Philippines, there is an urgent need to expand the clinical services for diagnosis, management and emotional support for patients with genetic conditions and their family members. Despite the lack of trained providers with specialization in genetics, public health related geneticsprograms are continuously being implemented. These address these current demands,strategic planning began in 2009 between local medical geneticists and international genetic professionals to develop the curriculum for an advanced degree in genetic counseling program. The board of regents at the University of the Philippines approved the proposed curriculum in January 2011, and training of the Philippines first cohort of genetic counseling students commenced in June 2011. The successful implementation of the MS of Genetic Counseling program will provide the opportunity to incorporate the match needed genetic counseling services in the country.

Mutations of the steroid 21-hydroxylase gene among Filipino patients with congenital adrenal hyperplasia

Congenital adrenal hyperplasia (CAH), an autosomal recessive disorder, is due to deficiency of the enzymes involved in adrenal steroidogenesis. Phenotypic manifestations vary as a result of the degree of glucocorticoid or mineralocorticoid deficiency and androgen excess present. Among Filipinos, the estimated crude incidence of CAH is approximately 1 in 7,000, which is higher than what is reported in most populations. More than 90% of all cases result from a 21-hydroxylase (21-OH) (cytochrome P450c21) enzyme deficiency involving two 21-OH genes, the active gene (CYP21) and a pseudogene (CYP21P). Studies have shown that mutations result from unequal crossover during meiosis which leads to complete deletion of the gene, gene conversion events or to point mutations. To date, there are no published data on the types of mutations present among Filipinos diagnosed with congenital adrenal hyperplasia. The objective of this study is to describe the profile of Filipino patients diagnosed with CAH and to determine the disease-causing alleles in the 21-OH gene of these patients. Using a method of combined differential polymerase chain reaction and amplification created restriction site approach, direct probing for the presence of known mutations in exons 1,3,4,6,7,8 and intron 2 of the CYP21 and CYP21P genes among Filipino patients with CAH was performed. A total of 12 unrelated CAH patients were examined. A majority of these cases had a premature splicing error mutation at nucleotide 656 of intron 2. The determination of the most frequent alleles in our population can facilitate rapid screening for mutations in the 21-OH gene and lead to a definitive diagnosis of CAH.