Cytochrome P450 enzymes play a central role in the phase I biotransformation process of a wide range of compounds, including xenobiotics, drugs, hormones and vitamins. It is noteworthy that these enzymes are highly polymorphic and, depending on the genetic makeup, an individual may have impaired enzymatic activity. Therefore, the identification of genetic variants in these genes could facilitate the implementation of pharmacogenetic studies and genetic predisposition to multifactorial diseases. We have established the frequencies of CYP2B6 (rs3745274; rs2279343) and CYP3A4 (rs2740574) alleles and genotypes in 209 healthy Malian subjects using TaqMan drug metabolism genotyping assays for allelic discrimination. Allele frequencies were 37% for CYP2B6 rs3745274; 38% for CYP2B6 rs2279343; and 75% for CYP3A4 rs2740574 respectively. Overall, the frequencies observed in Mali are statistically comparable to those reported across Africa except North Africa. The major haplotypes in CYP2B6 rs3745274 and CYP2B6 rs2279343 were represented by GA (60.24%) followed by TG (35.36%). We noted a strong linkage disequilibrium between CYP2B6 rs3745274 and CYP2B6 rs2279343 with D' = 0.91 and r2 = 0.9. The frequencies of the genotypic combinations were 43.5% (GT/AG), 37.3% (GG/AA) and 11.5% (TT/GG) in the combination of CYP2B6-rs3745274 and CYP2B6-rs2279343; 26.8% (GT/CC), 25.4%, (GT/CT), 17.2% and GG/CT in the combination CYP2B6-rs3745274-CYP3A4-rs2740574; 26.8% (AG/CC), 23.9% (AA/CC), 19.1% (AG/CT), and 11% (AA/CT) in the combination CYP2B6-rs2279343-CYP3A4-rs2740574, respectively. The most common triple genotype was GT/AG/CC with 24.9%, followed by GG/AA/CC with 23.9%, GT/AG/CT with 16.7%, and GG/AA/CT with 10%. Our results provide new insights into the distribution of these pharmacogenetically relevant genes in the Malian population. Moreover, these data will be useful for studies of individual genetic variability to drugs and genetic predisposition to diseases.
BACKGROUND: Apolipoprotein E (apoE) is encoded by a polymorphic gene located on chromosome 19. The three common apoE alleles are epsilon2, epsilon3 and epsilon4. We studied the frequencies of the apoE alleles and genotypes in the three ethnic groups-Malay, Chinese and Indian-in Malaysia using DNA amplification followed by agarose gel electrophoresis.
METHODS: EDTA blood was collected and DNA was extracted using proteinase K-SDS digestion and purified by phenol-chloroform extraction. The apoE gene sequence was amplified using the PCR and apoE genotyping was performed by restriction enzyme digestion with HhaI.
RESULTS: Genotyping of the apoE gene produces six genotypes-E2/E2, E2/E3, E3/E3, E2/E4, E3/E4 and E4/E4. The most common apoE genotype in the Malays, Chinese and Indians studied was E3/E3, thus the most common apoE allele was epsilon3. The three common apoE genotypes were E3/E3 followed by E3/E4 and E2/E3, except in the Indians where E2/E3 was not detected. The three apoE alleles were confirmed in the Malays, Chinese and Indians except for the epsilon2 allele which was absent in the Indians.
CONCLUSION: The combined frequency of the apoE alleles in the Malays, Chinese and Indians was 0.058, 0.829 and 0.114 for epsilon2, epsilon3 and epsilon4, respectively.
Primary biliary cirrhosis (PBC) is uncommonly described from Asia and it is an extremely rare cause of chronic liver disease in India. Six first generation migrant Asian patients with PBC were seen at the Liver Unit, Queen Elizabeth Hospital, Birmingham during the period 1982-94. All were women and their ages at presentation ranged from 31 to 63 (median 40) years. All were symptomatic for a median of 6 months prior to referral to the unit for transplantation. Itching with or without jaundice was a common presenting feature. Diagnosis was based on raised serum IgM levels, presence of antimitochondrial antibody (titres 100-400) and diagnostic histology. Only one patients had an associated autoimmune disease (coeliac disease). Serum bilirubin level was above 100 mumol/l at the time of presentation in four patients. Four of these patients with end-stage PBC are first generation migrants from south Asia, who have been resident in the West Midlands for the past 10 to 34 years. The total south Asian population of the West Midlands is 276,754; thus, from these four patients alone the estimated prevalence of PBC in the migrant south Asian population is at least 14 per million. However, such data cannot be used to give any accurate assessment of prevalence, for which a population screening programme is required. A higher incidence in the migrant population than in their countries of origin is compatible with an environmental aetiology.
Genetic polymorphisms of CYP2C9 among different populations in different geographical regions could be different. CYP2C9 has been reported to be the enzyme responsible for the metabolism of many drugs, including warfarin and other drugs with a narrow therapeutic index. Realising the importance of inter-individual differences in the genetic profile in determining the outcome of a drug therapy, this study was conducted to explore the types and frequencies of CYP2C9 alleles in healthy and warfarin-treated Malays and Chinese, the two major ethnic groups in Malaysia. We aimed to evaluate the prevalence of the types and frequencies of common CYP2C9 alleles (*1, *2, *3 and *4) among the healthy unrelated individuals and diseased patients prescribed with warfarin.
INTRODUCTION: This study was undertaken to establish the craniofacial anthropometric norms of young adult Malaysian Malays.
METHODS: The study group consisted of convenient samples of 100 healthy volunteers (aged 18-25 years), with an equal number of female and male subjects who had no history of mixed racial parentage. 22 linear measurements were taken twice from 22 landmarks over six craniofacial regions.
RESULTS: The Malays shared many similar sizes of measurements with the Singaporean Chinese. Their left eye fissure length and mouth width (ch-ch) were almost identical for both genders. However, Malay females had an upper lip height (sn-sto) (left) and ear width (pra-pa) similar to Singaporean Chinese females. Six other measurements, viz. the head width (eu-eu), head circumference (on-op), face height (n-gn), lower face height (sn-gn), (left) eye fissure height (ps-pi), cutaneous upper lip height (sn-ls) and cutaneous upper lip height (ls-sto), were 0.4-4.3 mm less in the Malays. Measurements for another four parameters, viz. the length of the head (g-op), biocular width (ex-ex), lower vermillion height (sto-li) and (left) ear length (sa-sba), were 0.5-3.6 mm higher in the Malays. Only three measurements were obviously different; the height of the head (v-n) and intercanthal width (en-en), were lower, and the protrusion of the nasal tip (sn-prn) was higher in the Malays.
CONCLUSION: These findings suggest that three features, i.e. the height of the head (v-n), intercanthal width (en-en) and protrusion of the nasal tip (sn-prn) may be useful in differentiating a Malay face from a Singaporean Chinese one.
Micropenis may be an important sign of underlying hypogonadism or pituitary hypofunction in the neonatal period. Penile lengths of normal newborns have been reported in many Western populations. However, the data may not be applicable in the Asian or the multiracial Malaysian population. Our study aimed to establish the normal penile length and testicular volume in term newborn infants in the major ethnic groups in Malaysia.
The study was conducted to determine the pick-up rate of abnormal cervical smears and the prevalence rate of cervical cancer in women aged 60 years and above and the demographic characteristics of the women screened. The pick-up rate of abnormal cervical smears was 1.65%. The prevalence rate for cervical intraepithelial neoplasia and frank carcinoma was 6.4 and 5.0 per thousand women screened respectively. The study group comprised 89.7% Chinese, 4.7% Malays, 3.6% Indians and 2.0% Others. The pick-up rate of abnormal smears was 1.9% in the Chinese and 1.3% in the Indians. There were no abnormal smears in the Malays and Others. The results demonstrate the importance of a routine cervical cancer screening programme among elderly women aged 60 years and above in Singapore.
Two of the four patients with tropical venereal diseases underwent incision and drainage of the inguinal bubo resulting in discharging sinus before they were referred to the Skin Clinic. Clinical diagnosis was made in all four but could not be confirmed. With appropriate therapy resolution was achieved without complications. The difficulties in arriving at and establishing the diagnosis are discussed.
Study site: Department of Dermatology
Sultanah Aminah General Hospital
Computerised data of 110,236 Singaporean males aged 15 to 25 (mean 17.75) years who underwent compulsory medical examination from April 1987 to January 1992 were used to estimate the prevalence and severity of myopia among young Chinese, Malay, Indian and Eurasian Singaporean males with different educational levels. The prevalence and severity of myopia amongst the groups with different educational levels were compared. These groups were fairly well-matched for important known confounding factors such as age, sex, race and degree of urbanisation of place of residence. Our data showed a positive association between educational attainment and both the prevalence and severity of myopia. Both the prevalence of myopia and the proportion of myopes with severe myopia were in general higher among those with more years of formal education.
Noninvasive oximetry provides continuous monitoring of arterial oxygen saturation and hence, early detection of hypoxia. This has proved to be a useful adjunct to patients' safety, and is considered indispensable in certain settings. However, errors may be present in the pulse oximeter estimation (SpO2) of arterial oxygen saturation (SaO2), which may be due to various parameters. We have studied a multi-ethnic population where the skin pigmentation is different, and also under different conditions comparing SpO2 with SaO2. Our results showed that SpO2 estimation of SaO2 amongst the three racial groups (Chinese, Malays, and Indians) varied significantly (ANOVA, p < 0.05). The over-estimation was more pronounced by hypoxic conditions and jaundice. Haemoglobin and systolic blood pressure did not affect the difference between SpO2 and SaO2.
The birth weight distribution, mean birth weight and incidence of LBW amongst the various ethnic groups in Malaysia is described briefly. The data collected and analysed is hospital data where all deliveries in 1980 were analysed. The mean birth weight showed that the Chinese had the highest Mean Birth Weight amongst the three ethnic groups and the Indians had the lowest mean birth weights. The overall incidence of LBW was 11.8% and the Malay and Indian babies constituted the high
incidence of LBW whereas the Chinese had a low incidence of LBW babies in the study. Amongst the various ethnic groups the Indians had a higher incidence of LBW compared to the Chinese and Malays.
Cardiomyopathy developed in the peripartum period in two healthy primigravida at 41 and 42 weeks of gestation are presented. In the first case, the patient presented with pulmonary oedema and had cardiac arrest immediately after admission. After resuscitation, a live baby was delivered by Caesarean section. Second cardiac arrest occurred after 12 hours of operation and the patient was resuscitated again. On the 8th post operative day, patient died of D.I.V.C. and renal failure. The second case was a twin pregnancy associated with pregnancy induced hypertension. Caesarean section was performed for foetal distress. She developed pulmonary oedema with left ventricular failure on the second post operative day, was resuscitated and discharged on the 15th day. These are the first two cases to be reported from Hospital University Sains Malaysia. Reference is made to three other cases in which a similar pathological process might have occurred.
Cardiorespiratory adjustments to maximal treadmill exercise were studied in young untrained Malaysia men representative of the three major ethnic groups in Malaysia and Singapore. Maximal values for oxygen uptake and cardiac performance were essentially similar In the three groups and were comparable to those reported for other populations.
Diabetes mellitus is a common chronic disease in Singapore. Its occurrence in pregnant women was 1.3% in a previous report. In a survey of 145 consecutive pregnant women registered at Alexandra Hospital the incidence of gestational diabetes was 13.1% when a total screen with 75 gm oral glucose challenge was used. The mean age of this sample was 27 years and the mean gestation at screening 33 weeks. There was an excess of Malay and Indian patients. Fifty percent had traditional risk factors tor gestational diabetes. Whether this higher incidence is a result of more stringent screening and/or increased occurrence remains to be confirmed.
83 Malays with HbE beta-thalassaemia who were not transfusion dependent were investigated. 79 persons showed no beta0 formation indicating the predominant gene in Malays with HbE beta-thalassaemia was beta0. HbF assays showed levels that were similar to transfusion dependent patients. Further studies are necessary to determine the presence of the alpha, (alpha+) gene Interacting with HbE and beta0 to produce the milder phenotype of HbE beta-thalassaemla.
We report a retrospective study of all cases of toxic epidermal necrolysis admitted to the adult medical wards of the University Hospital in Kuala Lumpur over a 16 year period from 1967 to 1983. Over this period of time only 7 cases were encountered, suggesting the condition is rare in adults in our country. All the cases were females and the age ranged from 21 to 41 years. Four cases were due to drugs, 2 were idiopathic and one was attributed to Staphylococcal infection. One patient died. The other patients recovered completely with no sequelae.