Thai Subjects Research Articles

Identification of Hb Q-India (64 Asp→His) in Thailand

More than 30 different hemoglobin variants either affecting  or β globin chains have been identified in Thailand. The large variety in the different forms of hemoglobinopathy contributes to several complicated interactions, since different types of defective globin alleles are prevalent in Thailand and nearly 30-40% of the population are carriers of either  or β thalassemia (thal). Many rare and novel abnormal globin variants in Thai subjects have been identified in our laboratory within the past few years; including Hb Lepore-Hollandia, homozygous Hb Tak, Hb Dhonburi, Hb G-Makassar, Hb G-Coushatta, Hb New York, Hb Paksè and Hb Pak Num Po. In addition to these, here we report, for the first time, the identification of Hb Q-India, an innocuous  globin variant, in a Thai family with Indian ancestry. This report highlights the complexity associated with identifying unknown globin variants within a population that has a heterogeneous repertoire of globin chain disorders.

URINARY 2-HYDROXYFLUORENE AND 1-HYDROXYPYRENE LEVELS IN SMOKERS AND NONSMOKERS IN JAPAN AND THAILAND

2-Hydroxyfluorene (2-OHF) and 1-hydroxypyrene (1-OHP) in urine samples of smokers and nonsmokers were determined separately by using two high-performance liquid chromatography (HPLC) systems with fluorescence detection. Urine samples were collected from the subjects who lived in Japan and Thailand, and were not occupationally exposed to polycyclic aromatic hydrocarbons (PAHs). The mean concentrations of 2-OHF and 1-OHP of Thai smokers (0.75 and 3.03 μmol/mol creatinine) and nonsmokers (0.22 and 0.91 μmol/mol creatinine) were both higher than those of Japanese smokers (0.26 and 0.12 μmol/mol creatinine) and nonsmokers (0.04 and 0.06 μmol/mol creatinine), respectively. The difference between smokers and nonsmokers was more significant for 2-OHF than for 1-OHP, reflecting the higher intake of fluorene in the vapor phase by the smoking. Moreover, the higher urinary levels of both 2-OHF and 1-OHP were observed in Thai nonsmokers than those in Japanese nonsmokers, suggesting the higher background exposure to PAHs of Thai subjects.

Distribution of interleukin-1beta(+3954) and IL-1alpha(-889) genetic variations in a Thai population group.

The severe form of chronic periodontitis (CP) has been reported to be strongly associated with the presence of allele 2 of composite IL-1beta(+3954) and IL-1alpha(-889) genetic polymorphisms (genotype positive). However, other studies have reported conflicting findings, not only on the association between the composite IL-1 gene polymorphisms and CP, but also the link between IL-1 gene polymorphisms and aggressive periodontitis (AgP). These might have resulted from differences in ethnic background and disease entities. The aim of this study was to determine the distribution of IL-1beta(+3954) and IL-1alpha(-889) genetic polymorphisms in a group of Thai subjects based on their periodontal status, including CP, AgP, and healthy groups. A total of 123 Thai subjects were clinically and radiographically assessed for their periodontal status. Blood samples were collected by fingerstick and adsorbed onto filter paper. The IL-1beta(+3954) and IL-1alpha(-889) genotypes were performed by polymerase chain reaction, digested with restriction enzymes, and separated by gel electrophoresis. The distribution of allele 1 homozygous genotype was 97.6% and 84.6% for IL-1beta(+3954) and IL-1alpha(-889), respectively. No allele 2 homozygous genotype was detected in either of these two gene loci. Only 1.6% (2 out of 123) of the subjects were genotype positive, which was too low to determine the association between the composite genotype of IL-1beta(+3954) and IL-1alpha(-889) and severe forms of periodontal disease. Genetic polymorphism of IL-1 genes in these two loci may not be useful in predicting the severity of periodontal disease in the Thai ethnic group.

Gene frequencies of the HPA-1 to HPA-13, Oe and Gov platelet antigen alleles in Taiwanese, Indonesian, Filipino and Thai populations.

Human platelet antigen (HPA) systems consist of more than twelve bi-allelic antigen polymorphisms in which a base pair substitution leads to change in an amino acid of a glycoprotein expressed on the platelet. The neonatal alloimmune thrombocytopenia (NAIT), post transfusion purpura, and refractoriness to platelet transfusion can be induced by antibodies against human platelet antigens: e.g. HPA-1a, 3a, 4a, 5a, and Gova. HPA typing is essential for the diagnosis and treatment of a variety of diseases. We developed a PCR-based method to detect HPA-1 to HPA-13, Oe and Gov platelet alloantigens. In this method, the amplified PCR products were used to recognize the polymorphism after restriction enzyme digestions. Among 566 Taiwanese, 107 Indonesian, 100 Filipino and 137 Thai subjects studied, HPA-1a, 2a, 4a, 5a, 6a, 7aW, 8aW, 9a, 10a, 11a, 12a, 13a, Oea genes were present in every sample; while HPA-1b, 2b, 4b, 5b and 6b were rarely found. HPA-7aW, 8aW, 9, 10, 11, 12, 13, and Oea alleles were noted to be monomorphic only. HPA-3a/3b alleles had frequencies of 0.595/0.405, 0.505/0.495, 0.507/0.493, 0.530/0.470, while Gova/Govb of 0.462/0.538, 0.450/0.550, 0.463/0.537, 0.520/0.480 among Taiwanese, Indonesians, Thais and Filipinos respectively. The prevalence rates of HPA-1 to 13 in this study were also consistent with other previous reports using different methods. The alloimmunization due to Gov and HPA-3 antigens need to be emphasized in these populations.

Pharmacokinetics of indinavir/ritonavir (800/100 mg) in combination with efavirenz (600 mg) in HIV-1-infected subjects.

Addition of efavirenz (600 mg) to indinavir/ritonavir (800/100 mg) results in significant decreases in indinavir levels in healthy volunteers. This study evaluated the steady-state pharmacokinetics of indinavir/ritonavir at 800/100 mg twice daily (bid) in combination with efavirenz at 600 mg once daily (qd) in HIV-infected Thai subjects who used this nucleoside-sparing combination in The HIV Netherlands Australia Thailand Research Collaboration 009 study. At week 4 of the study, 12-hour pharmacokinetic profiles for indinavir/ritonavir were obtained for 20 HIV-infected subjects. For efavirenz, the concentrations at 12 hours and 24 hours (Cmin) after dosing were assessed. All subjects (10 males and 10 females) completed the study. The geometric mean area under the concentration versus time curve, Cmin, and maximum plasma concentration of indinavir were 45.7 mg/(L. h) (95% confidence interval [CI], 39.8-52.5), 0.32 mg/L (95% CI, 0.24-0.44), and 11.1 mg/L (95% CI, 9.4-13.0), respectively. A >10-fold variation in indinavir Cmin was observed. All subjects had an indinavir Cmin that was at least comparable with the reported mean population Cmin of indinavir at 800 mg thrice daily without ritonavir (0.15 mg/L). The geometric mean concentration at 12 hours and Cmin of efavirenz were 3.1 mg/L (95% CI, 2.5-3.7) and 2.1 mg/L (95% CI, 1.6-2.6), respectively. Despite the known pharmacokinetic interaction between efavirenz and indinavir/ritonavir, the combination of indinavir/ritonavir at 800/100 mg bid and efavirenz at 600 mg qd results in adequate minimum concentrations of both indinavir and efavirenz for treatment-naive patients.

Thailand

Thailand, the land of smiles, is about the size of France but with the population of the UK (65 million), located in the middle of South-East Asia. The northern part...

Helicobacter pylori Infection, Mucosal Atrophy and Intestinal Metaplasia in Asian Populations: A Comparative Study in Age‐, Gender‐ and Endoscopic Diagnosis‐Matched Subjects

It is known that the incidence and mortality rate of gastric cancer is high among Japanese and Chinese populations, but extremely low in Thai and Vietnamese populations. The aim of this study was to investigate the prevalence of Helicobacter pylori infection and the differences in the glandular atrophy and intestinal metaplasia scores in stomach specimens of Asian adult subjects of different races. Chinese, Thai, Vietnamese and Japanese patients were matched by age, gender and endoscopic diagnosis, in order to compare the differences in incidence of H. pylori-related peptic ulcer disease and the prevalence of H. pylori infection among four Asian populations (n = 700). Glandular atrophy scores and intestinal metaplasia scores were also compared among four Asian populations divided into H. pylori-positive cases (n = 120, 109, 145, 80, respectively) and H. pylori-negative cases (n = 55, 66, 30, 95, respectively). Among peptic ulcers, gastric ulcer was more frequently seen in Japanese subjects than in the other Asian populations examined. On the other hand, duodenal ulcer was more frequently seen in other Asian populations than in Japanese subjects. The prevalence of H. pylori infection was similar in the Japanese (Tokyo) and Chinese (Beijing and Fuzhou) populations. It was higher in Thai (Chiang Mai) subjects compared with Japanese subjects. On the other hand, Vietnamese (Ho Chi Minh) subjects had significantly lower rates of H. pylori infection than Japanese subjects. The glandular atrophy and intestinal metaplasia scores in the stomach were significantly higher in the H. pylori-positive Japanese subjects than in H. pylori-positive subjects belonging to other Asian populations, except for the higher glandular atrophy scores in Chinese rather than Japanese subjects. On the other hand, there were no significant differences in the glandular atrophy and intestinal metaplasia scores in the angulus of the stomach among H. pylori-negative subjects belonging to the different Asian populations examined. Gastric ulcer was more common among Japanese subjects, while duodenal ulcer was more common among the other Asian populations examined. Japanese subjects with H. pylori infection showed more severe atrophic and metaplastic gastritis compared with that in other Asian subjects with H. pylori infection. These results may be related to the higher incidence of gastric cancer noted in Japanese subjects and the lower incidence of the cancer seen in Thai and Vietnamese patients.

Potassium depletion in a healthy north-eastern Thai population: no association with tubulo-interstitial injury.

Potassium depletion prevails among the healthy population of north-east Thailand, as well as among patients with certain metabolic disorders such as upper urinary tract stones, the sudden unexplained death syndrome, distal renal tubular acidosis and hypokalaemic periodic paralysis. However, definite proof of the relationship of potassium depletion and these metabolic disorders is lacking. We prospectively studied muscle and kidney potassium content including renal tissue pathology in three groups of healthy adult Thai subjects who died of vehicular accidents. Group 1 (n = 24) were Bangkok city dwellers; groups 2 (n = 10) and 3 (n = 22) lived in north-eastern Thailand in the metropolitan area and in the villages, respectively. The muscle potassium content of group 1 (338.5 +/- 9.6 mEq/kg dry weight (DW)) were similar to group 2 (307.9 +/- 11.9 mEq/kg DW), but was greater than group 3 (295.4 +/- 9.1 mEq/kg DW; P < 0.01). The kidney potassium content of group 1 (208.6 +/- 7.8 mEq/kg DW) was significantly higher than group 3 (175.9 +/- 6.3 mEq/kg DW, P < 0.05). In group 3, the muscle potassium correlated linearly with the kidney potassium (r = 0.455, P = 0.33). None of the group 3 patients had renal histopathological change compatible with a diagnosis of focal or diffuse interstitial nephritis. This study confirms that potassium depletion is common among healthy rural dwellers in north-east Thailand. This deficit was probably chronic. However, there was minimal renal tubulo-interstitial change.

Analysis of β‐Thalassemia Mutations in Northern Thailand Using an Automated Fluorescence DNA Sequencing Technique

A total of 218 β‐thalassemia (thal) genes from 109 β‐thal major patients were characterized using an automated fluorescence DNA sequencing technique. Eight different mutations were identified in all 218 alleles (100%). Four common mutations accounted for 96.8% [49.5% were codons 41/42 (–TTCT), 34.4% were codon 17 (A→T), 6.9% were IVS‐I‐1 (G→T) and, 6.0% were codons 71/72 (+A)]. There were three cases of −28 (A→G) and one of IVS‐II‐654 (C→T), mutations that have been previously described in Thai subjects. We also identified two mutations in the β‐globin promoter region which have not been reported in Thailand before [−31 (A→G) and −87 (C→A)]. Although these mutations are described as β+‐thal, the compound heterozygote with one of the common β0‐thal mutations exhibits the phenotype of β‐thal major. The frequency of β‐thal genes in northern Thailand were similar to the northeastern region, but different from those reported in southern and central Thailand, where IVS‐I‐5 (G→C) and IVS‐II‐654 (C→T) were the second most common anomalies, respectively. The spectrum of β‐globin gene mutations from this study will be useful for planning a prenatal diagnosis program especially for this region of Thailand.

Neural circuitry underlying perception of duration depends on language experience

Thai, a language which exhibits a phonemic opposition in vowel length, allows us to compare temporal patterns in linguistic and nonlinguistic contexts. Functional MRI data were collected from Thai and English subjects in a speeded-response, selective attention paradigm as they performed same/different judgments of vowel duration and consonants (Thai speech) and hum duration (nonspeech). Activation occurred predominantly in left inferior prefrontal cortex in both speech tasks for the Thai group, but only in the consonant task for the English group. The Thai group exhibited activation in the left mid superior temporal gyrus in both speech tasks; the English group in the posterior superior temporal gyrus bilaterally. In the hum duration task, peak activation was observed bilaterally in prefrontal cortex for both groups. These crosslinguistic data demonstrate that encoding of complex auditory signals is influenced by their functional role in a particular language.

Relationships of body fat distribution, insulin sensitivity and cardiovascular risk factors in nonobese, nondiabetic Thai subjects

Relationships of body fat distribution, insulin sensitivity and cardiovascular risk factors in nonobese, nondiabetic Thai subjects

A Simplified Screening for α-Thalassemia 1 (SEA Type) Using a Combination of a Modified Osmotic Fragility Test and a Direct PCR on Whole Blood Cell Lysates

In order to provide a rapid method for identifying α-thalassemia 1 in a region with massive population and limited resources, we have tested a rapid screening strategy. Preliminary screening was done using a modified onetube osmotic fragility test (OF test) followed by RBC indices; Hb analysis and detection of α-thalassemia 1 with the Southeast Asian deletion (SEA type) were performed by PCR. One hundred and seventy-five adult Thai subjects were studied. Fifty-one of the 175 subjects (29.1%) were positive for a modified OF test. They all had significantly lower MCV and MCH but higher RDW-CV values as compared to the OF negative group. A successful identification of α-thalassemia 1 deletion using a direct PCR on cell lysates was demonstrated. Among the 51 OF-test-positive subjects, 7 were found to be α-thalassemia 1 carriers, 3 of whom were also carriers of Hb E. No α-thalassemia 1 was detected in the OF-test-negative group. A combination of a modified OF test and a direct PCR analysis on whole blood cell lysates would therefore provide an effective screening for α-thalassemia 1 in the regions where a program of prevention and control of the disease remains underserved.

Gene frequencies of the HPA-1 to HPA-8w platelet antigen alleles in Taiwanese, Indonesian, and Thai.

Human platelet antigen (HPA) systems consist of more than eight biallelic antigen polymorphisms in which a base pair substitution leads to change in an amino acid of a glycoprotein expressed on the platelet. HPA typing is essential in the diagnosis and treatment for a variety of diseases. We developed a polymerase chain reaction (PCR)-based method to detect HPA-1 through HPA-8w. In this method, the amplified PCR products were used to recognize the polymorphism after restriction enzyme digestions. Among 295 Taiwanese, 107 Indonesian, and 137 Thai subjects studied, HPA-1a, 2a, 4a, 5a, 6a, 7aw, and 8aw genes were present in every sample tested. HPA-1b, 2b, 4b, 5b, and 6b were rarely found among subjects. Only monomorphic HPA-7aw and 8aw alleles were noted in the samples. HPA-3a and 3b alleles showed frequencies of 0.595/0.405, 0.504/0.496, and 0.507/0.493 in Taiwanese, Indonesian, and Thai subjects, respectively. Our report is the first PCR-based method to detect most of the HPA antigen variants in Taiwanese, Indonesian, and Thai. The genomic typing results were also confirmed by direct sequencing for uncertain and some representative cases. The prevalence rates of HPA-1, 2, 3, 4, and 5 in this study were also consistent with other previous reports using different methods.

Genetic variations of human herpesvirus 7 by analysis of glycoproteins B and H, and R2-repeat regions.

Clinical isolates of human herpesvirus 7 (HHV-7) from the saliva of healthy individual were investigated for genetic variations in the regions of two immediate-early (IE) genes, the glycoprotein B (gB) and glycoprotein H (gH) genes, and in R2-repeat. The genomic DNA of 24 isolates from citizens of Thailand, Japan, and the United States was amplified to detect size variations in the IE-1 and IE-2 loci, but none was observed, suggesting that there was no deletion or insertion in these genes, in contrast with an IE gene of human herpesvirus 6 (HHV-6). The sequences of the gB gene from isolates acquired from 5 Japanese and 8 Thai subject were then compared with those of American strains JI and RK with respect to codons that are known to differentiate gB alleles. All the isolates were found to have gB allele C except for the JI strain, which has allele F. Variability was also observed in five specific gH codons, resulting in 6 different groups. The HHV-7 isolates might be classified into two major genetic variants by combining their gB and gH allelic groupings. In the present study, only JI belonged to variant 1, while the rest of the isolates appeared to belong to variant 2. In the R2-repeat region, size heterogeneities were observed among the 24 isolates, due to different repeat numbers (17, 15, 14, 13, or 12 repeats). Therefore, we used the R2-repeat to identify the origins of isolates in a study of HHV-7 transmission, and found HHV-7 to be transmitted within a family from both mothers and fathers to their children.

A Mutation in the Flavin-containing Monooxygenase 3 Gene and its Effects on Catalytic Activity for N-oxidation of Trimethylamine In Vitro

To clarify the mutation of the flavin-containing monooxygenase (FMO) 3 gene causing fish-odor syndrome, we analyzed the FMO3 gene of a Thai subject who possibly suffered from fish-odor syndrome. A novel mutation, a single-base substitution from G to A at the position of 265 (G265A), was identified in exon 3. The mutation caused an amino acid substitution from valine to isoleucine at residue 58 (V58I). The mutated FMO3 protein with V58I exhibited the reduced trimethylamine N-oxidase activity when it was expressed in E. coli. The V(max)/K(m) value for the activity of the mutant-type FMO3 was about 5 times lower than that for the wild-type FMO3.

Hb Paksé [(α2) CODON 142 (TA A→TA T OR Term→Tyr)] IN THAI PATIENTS WITH EABart's DISEASE AND Hb H DISEASE

Hb Paksé is caused by an α2-globin gene termination codon mutation, TA A→TA T or Term→Tyr, initially described in a Laotian family. We now report for the first time that the same mutation has been found in 14 Thai patients, seven with EABart's disease, four with Hb H disease, and three with α-thalassemia trait who were initially diagnosed as having Hb Constant Spring (Hb CS; α2-globin gene termination codon mutation T AA→C AA or Term→Gln). Co-inheritance of this mutation with α-thalassemia-1 (SEA type) leads to Hb H disease (hereafter designated as Hb H-Paksé disease) and to a complex thalassemia syndrome, namely EABart's-Paksé disease. Hematological data of these patients were compared with those of classical Hb H-CS and the EABart's patients. To facilitate epidemiological and diagnostic screening of Hb Paksé, a simple assay procedure based on allele specific polymerase chain reaction (PCR) amplifications was developed and validated. Using this allele specific PCR as a screening method, five additional individuals with Hb Paksé were found among 71 Thai subjects previously thought to have Hb CS.

A Double-Blind, Adjuvant-Controlled Trial of Human Immunodeficiency Virus Type 1 (HIV-1) Immunogen (Remune) Monotherapy in Asymptomatic, HIV-1-Infected Thai Subjects with CD4-Cell Counts of &gt;300

A Double-Blind, Adjuvant-Controlled Trial of Human Immunodeficiency Virus Type 1 (HIV-1) Immunogen (Remune) Monotherapy in Asymptomatic, HIV-1-Infected Thai Subjects with CD4-Cell Counts of &gt;300

Detection and quantification of HIV type 1 RNA in nasopharyngeal washes from HIV-infected subjects.

Human immunodeficiency virus type 1 (HIV) RNA load was measured in paired samples of peripheral blood plasma and nasopharyngeal (NP) washes from 97 Thai subjects infected with subtype E or B. HIV RNA was quantifiable in 93% of peripheral blood plasma samples tested and was inversely correlated (rho =-0.524; p < 0.001) with CD4 absolute count. HIV RNA was quantifiable in 29% of NP samples tested, and the median value was less than that of plasma viral load. HIV RNA load in NP samples was correlated (rho = 0.388; p < 0.001) with viral load in peripheral blood. HIV RNA was not detected in NP washes from subjects with undetectable plasma viral load. Virus isolation attempts on two NP samples were negative. The results do not support local HIV production in the nasopharynx, but extend current knowledge of HIV shedding to include the NP compartment.

Haplotype analysis at the FRAXA locus in Thai subjects

The prevalence of fragile X syndrome (FXS) is approximately 7% in Thai boys with developmental delay of unknown cause. To determine if FXS might have a specific haplotype association, we analyzed 125 unrelated control subjects and 25 unrelated FXS patients using 3 microsatellites, DXS548, FRAXAC1 and FRAXE, and two single nucleotide polymorphisms, ATL1 and IVS10. FRAXAC1 and DXS548 are located ∼7 kb and ∼150 kb proximal to the CGG-FMR1 whereas ATL1, IVS10 and FRAXE are located ∼5.6 kb, ∼24.5 kb and ∼600 kb distal to the CGG-FMR1. We found 40 haplotypes in the control group and 14 haplotypes in the FXS group. Of 14 haplotypes in the FXS group, 6 haplotypes were not found in the control group suggesting possible new mutations or admixture of immigrant haplotypes. We observed that most diverse haplotypes came from different FRAXE alleles. For this reason, we analyzed haplotypes composed from the remaining markers alone (DXS548-FRAXAC1-ATL1-IVS10). We found 2 major haplotypes (20-18-G-T and 20-19-A-C) with no significant haplotype differences between the control group (67/125 of 20-18-G-T and 25/125 of 20-19-A-C) and FXS group (16/25 of 20-18-G-T and 6/25 of 20-19-A-C). The other haplotypes found were 33/125 in the control group and 3/25 in the FXS group. The two major haplotypes associated FXS in Thai subjects were the two most common haplotypes in the normal Thai subjects. We could not prove, therefore, that there were founder effects at the FRAXA locus in Thailand. We could not, however, exclude it completely. These findings apparently contrast with most other reports on FXS founder effects in various ethnic groups. © 2001 Wiley-Liss, Inc.

Haplotype analysis at the FRAXA locus in Thai subjects

The prevalence of fragile X syndrome (FXS) is approximately 7% in Thai boys with developmental delay of unknown cause. To determine if FXS might have a specific haplotype association, we analyzed 125 unrelated control subjects and 25 unrelated FXS patients using 3 microsatellites, DXS548, FRAXAC1 and FRAXE, and two single nucleotide polymorphisms, ATL1 and IVS10. FRAXAC1 and DXS548 are located approximately 7 kb and approximately 150 kb proximal to the CGG-FMR1 whereas ATL1, IVS10 and FRAXE are located approximately 5.6 kb, approximately 24.5 kb and approximately 600 kb distal to the CGG-FMR1. We found 40 haplotypes in the control group and 14 haplotypes in the FXS group. Of 14 haplotypes in the FXS group, 6 haplotypes were not found in the control group suggesting possible new mutations or admixture of immigrant haplotypes. We observed that most diverse haplotypes came from different FRAXE alleles. For this reason, we analyzed haplotypes composed from the remaining markers alone (DXS548-FRAXAC1-ATL1-IVS10). We found 2 major haplotypes (20-18-G-T and 20-19-A-C) with no significant haplotype differences between the control group (67/125 of 20-18-G-T and 25/125 of 20-19-A-C) and FXS group (16/25 of 20-18-G-T and 6/25 of 20-19-A-C). The other haplotypes found were 33/125 in the control group and 3/25 in the FXS group. The two major haplotypes associated FXS in Thai subjects were the two most common haplotypes in the normal Thai subjects. We could not prove, therefore, that there were founder effects at the FRAXA locus in Thailand. We could not, however, exclude it completely. These findings apparently contrast with most other reports on FXS founder effects in various ethnic groups.