RATIONALE: Among the first line antituberculosis (anti-TB) drugs, the major drug incriminated in the development of hepatotoxicity is isoniazid (INH). The human N-acetyl transferase2 (NAT2) gene is mainly responsible for INH metabolism. This gene exhibits a hereditarily determined polymorphism. There is presently no study on the predominant NAT2 genotype among Filipinos. There are also no Filipino studies on the incidence of hepatitis and other adverse effects of first line anti-TB drugs.

OBJECTIVES: To determine the predominant NAT2 genotype and its association with the development of hepatitis among Filipino children given first line anti-TB drugs (INH, rifampicin and pyrazinamide) and to determine the incidence of hepatitis and other serious adverse reactions to these drugs.

STUDY DESIGN: Prospective cohort study

SETTING: Tertiary government hospital in Metro Manila

STUDY POPULATION: Children on to 18 years old with pulmonary tuberculosis and normal liver function test at baseline.

METHODS: Total bilirubin (TB), direct bilirubin (DB) and liver transaminases (AST and ALT) were checked routinely at baseline and at thow, four, eight and 12 weeks after starting treatment. Within the first month of treatment, blood was also taken for NAT2 genotyping. The identification of the three NAT2 polymorphisms that are associated with a slow acetylator status - 481C to T (NAT2*5), 950G to A (NAT2*6) and 857G to A (NAT2*7) was carried out by polymerase chain reaction-restriction fragment length polymorphism. All patients were followed up for a total of six months. The presense of any adverse effects like gastroinstestinal symptoms, rash, hepatitis or drug fever was also monitored.

RESULTS: A total of 24 children [mean age: 5 years; 11 males] were included. Majority (96%) were diagnosed by passive detection and mean Z score was - 1.38 (1 to -3). No patient developed hepatotoxicity or any side effects to anti-TB drugs. In 23 patients who had NAT2 genotyping, 39% and 22% were alleles homozygous for the NAT2*6 and NAT2*7, respectively. There was a combination of alleles in only three (13%) subjects.

CONCLUSION: NAT2*6 and NAT2*7 alleles associated with a slow acetylator status were detected among our patients although the presence of these variants did not lead to any hepatotoxicity nor any treatment-related side effects. A larger study with broader genotype analysis is needed to confirm the present findings.

Human ; Male ; Female ; Adolescent ; Child ; Child Preschool ; Infant ; Isoniazid ; Pyrazinamide ; Rifampin ; Alleles ; Bilirubin ; Liver Function Tests ; Transaminases ; Antitubercular Agents ; Tuberculosis, Pulmonary ; Hepatitis ; Polymorphism, Genetic

INTRODUCTION: In the Philippines, lung, breast, colon-rectum, and oral cavity cancers are among the top 10 most common cancers. This study evaluates the risk factors for these cancers among Filipinos.

METHODS: This age-matched case-control study included incident primary cancers (histologically-diagnosed) of the lung, breast (also matched for sex), colon-rectum and oral cavity. Controls (clinically free and no history of cancer) were obtained from the same tertiary hospitals as the cases. Target sample size was 283 cases and 283 controls per cancer type. Conditional logistic regression was done.

RESULTS: Exposure to cigarette/tobacco was a significant risk factor for lung (OR of current smoker compared to non-smoker [95% Confidence Interval]: 3.6 [1.6-7.9]) and oral cavity cancers (2.0 [1.2-3.3]); family history (1st degree) for lung (4.3 [1.314.2]) and breast cancers (3.0 [1.2-7.5]); every year increase in age at first pregnancy for breast cancer (1.06 [1.02-1.11]). Other risk factors for oral cavity were passive smoking (2.8 [1.6-5.1]), chewing tobacco (5.2[1.4-19.5]) and inverted cigarette smoking (3.2[1.3-8.1]). Fish sauce (patis) was found to be a protective factor for breast cancer (0.34 [0.22-0.51]) and oral cavity (0.44 [0.25-0.78]) and use of shrimp paste (bagoong) (0.48 [0.27-0.84]) for oral cavity.

CONCLUSION AND RECOMMENDATIONS: Except for family history of cancer, the identified risk factors for lung, colon-rectum, and oral cavity cancers are preventable. Proper diet and lifestyle, avoidance of cigarettes and tobacco, and environmental safety in the workplace are key cancer prevention measures. Public awareness campaign and continuing healthcare provider education must always be part of a cancer prevention program.

Pregnancy ; Tobacco ; Tobacco, Smokeless ; Tobacco Smoke Pollution ; Cigarette Smoking ; Rectum ; Smokers ; Smoking ; Breast Cancer 3 ; Breast Neoplasms ; Mouth Neoplasms ; Health Personnel ; Colon

Introduction. Recurrent pregnancy loss is a devastating reproductive problem that affects 5% of couples trying to conceive. Majority of the cases are due to cytogenetic errors. This study determines the prevalence of chromosomal structural abnormalities in Filipino couples who presented with 2 or more pregnancy losses. Methods. Results from chromosomal analysis of couples referred for 2 or more miscarriages done at the Institute of Human Genetics-National Institutes of Health-University of the Philippines, Manila on peripheral blood samples from 1991 to 2010 were restrospectively reviewed. Results. There were 356 couples with a history of 2 or more miscarriages sent for chromosomal analysis from 1991-2010 included in this study. Among these 356 couples, 17 couples (4.8%) were found to be carriers of different chromosomal abnormalies. From a total of 18 cases, there were 13(3.6%) translocations, 1(0.3%) insertion, 2(0.6%) with marker chromosomes, 1(0.3%) pericentric inversion and 1(0.3%) deletion. Conclusion. The overall frequency of chromosomal structural abnormalities among patients with RPL in this study is 4.8% with translocations being the most common type detected. The results of this study are similar to that of previous large-scale studies which have demostrated that parental chromosomal abnormalities are associated with RPL.
Male ; Female ; RECURRENCE ; PREGNANCY ; CHROMOSOME ABERRATIONS ; ABORTION, SPONTANEOUS ; FEMALE UROGENITAL DISEASES AND PREGNANCY COMPLICATIONS ; PREGNANCY COMPLICATIONS ;

Introduction: Adiponectin is an adipocytokine known to have anti-inflammatory and anti-atherogenic effects. It appears to impact insulin resistance and the subsequent development of type 2 diabetes mellitus (T2D). The gene encoding adiponectin ADIPOQ, has single nucleotide polymorphisms (SNPs) that can be useful biomarkers to predict development of T2D; with the T/G polymorphism of SNP +45 in exon 2 being the most common. Objective: This study was conducted to evaluate the association of T45G adiponectin gene polymorphism with hyperglycemia among adult Filipinos seen at the outpatient department of the Philippine General Hospital. Methods: This is a matched case-control study, with duration of 12 months. DNA was extracted using the QIAGEN MIDI Blood Extraction Kit. The genomic DNA obtained was then subjected to real time PCR for SNP detection. Results: One hundred (100) adults were enrolled; forty-three (43) had normoglycemia, while fifty seven (57) had hyperglycemia, after a 75-g oral glucose tolerance test. Hyperglycemic subjects were older (44±15.6 years vs. 52±8.3 years, p-value 0.002), and had lower HDL levels (58.5±16.0 mg/dLvs. 47.8+11.8 mg/dL, p-value 0.000). Among thirty-nine (39) participants found to have the T45G adiponectin gene polymorphism, 22 or 56.4% were hyperglycemic while 17 or 43.6% were normoglycemic. Conclusion There was no significant association observed between the T45G SNP and presence of hyperglycemia.
Adiponectin ; Hyperglycemia

Oromandibular Limb Hypogenesis Spectrum (OMLHS) [OMIM 103300] is a rare disease characterized by congenital defects of the face, mandible, tongue and hypoplastic limbs. The exact etiology remains unknown. We present two Filipino children diagnosed with OLMHS. Patient 1 is a 2-year-old female noted to have micrognathia, sygnathia and hypoplasia of distal extremities. Patient 2 is a 6-year-old male with hypoplastic mandible, micrognathia, micromelia of both lower extremities and syndactyly of hands. The early recognition of this disease is important so that early surgical correction of deformities particularly the hypoplastic mandible be addressed to avoid complications such as respiratory distress and feeding difficulties.
Ankyloglossia ; Hanhart syndrome