Genetic profile of RHCE, Kell, Duffy, Kidd, Diego and MNS hybrid glycophorins blood groups in ethnic northeastern Thais: Alleles, genotypes and risk of alloimmunisation.

BACKGROUND: Antibodies against blood group antigens play a key role in the pathophysiology of haemolytic transfusion reactions (HTRs) and haemolytic disease of the fetus and newborn (HDFN). This study aimed to determine the frequencies of alleles, genotypes, and risk of alloimmunisation of clinically significant blood group systems in ethnic northeastern Thais. METHODS: In total, 345 unrelated, healthy, ethnic northeastern Thais were tested using the in-house PCR-sequence specific primers (PCR-SSP) method for simultaneously genotyping of RHCE, Kell, Duffy, Kidd, Diego and MNS glycophorin hybrids and results confirmed by Sanger sequencing. RESULTS: In this cohort, the alleles RHCE*C (81.0%) and RHCE*e (84.8%) were more prevalent than RHCE*c (19.0%) and RHCE*E (15.2%). The most common predicted haplotype combinations of the RHCE alleles were C+c-E-e+(R1R1) (59.4%) followed by the C+c+E+e+ (R1R2) (20.6%) and C+c+E-e+ (R1r) (11.3%). The KEL*01 allele was not found in this study. The frequencies of FY*01 and FY*02 were 88.3% and 11.7%, respectively. The genotype FY*02/02 was found in four samples (1.2%). The frequencies of JK*01 and JK*02 were 52.5% and 47.5%, respectively. Homozygous JK*02/02 was found in 81 samples (23.5%). The frequencies of DI*01 and DI*02 were 0.6% and 99.4%, respectively. In total, 64 samples (18.6%) were found to carry the MNS glycophorin hybrids. CONCLUSIONS: Our results indicated a possible high risk of c, E, Fyb, Jka, Jkb and Mia alloimmunisation in these populations. Moreover, methods established for genotyping clinically significant blood groups in this study can now be utilised in routine clinical application.

How an agreement with restriction of unhealthy food marketing and sodium taxation influenced high fat, salt or sugar (HFSS) food consumption.

BACKGROUND: Food taxation and food marketing policy are very cost-effectiveness to improve healthy diets among children. The objective of this study was to investigate the socio-demographic characteristics of Thais and attitude towards on policy unhealthy food marketing restriction and sodium taxation which influence high fat, sodium, and sugar (FHSS) food eating. METHODS: The data were obtained from the 2021 Health Behavior of Population Survey, four-stage sampling method of the Thai people, aged 15 years and above, using a offline survey application-assisted face-to-face interview. Logistic Regression were used to analyze the explanatory variables on agreement and HFSS food intake. RESULTS: Almost half (48.4%) of samples disagreed with sodium taxation, and 42.7% of the samples disagreed with food marketing restriction. Most (99.6%) of Thai respondents consumed HFSS food, including sugar sweetened beverages (SSB). Gender, age, education, income, BMI, and health status were associated with agreement with food marketing restriction policy and sodium taxation policy. There is no association between agreement with policy on sodium taxation and food marketing and HFSS food consumption. CONCLUSION: Nearly half of Thais indicated that they disagreed with policy on food marketing restriction and sodium taxation. Therefore, understanding and awareness of the two policies among Thais should be further investigated in order to develop better policy communication for increased public understanding and engagement.

Carrier frequency estimation of pathogenic variants of autosomal recessive and X-linked recessive mendelian disorders using exome sequencing data in 1,642 Thais.

BACKGROUND: People with autosomal recessive disorders often were born without awareness of the carrier status of their parents. The American College of Medical Genetics and Genomics (ACMG) recommends screening 113 genes known to cause autosomal recessive and X-linked conditions in couples seeking to learn about their risk of having children with these disorders to have an appropriate reproductive plan. METHODS: We analyzed the exome sequencing data of 1,642 unrelated Thai individuals to identify the pathogenic variant (PV) frequencies in genes recommended by ACMG. RESULTS: In the 113 ACMG-recommended genes, 165 PV and likely PVs in 60 genes of 559 exomes (34%, 559/1642) were identified. The carrier rate was increased to 39% when glucose-6-phosphate dehydrogenase (G6PD) was added. The carrier rate was still as high as 14.7% when thalassemia and hemoglobinopathies were excluded. In addition to thalassemia, hemoglobinopathies, and G6PD deficiency, carrier frequencies of > 1% were found for Gaucher disease, primary hyperoxaluria, Pendred syndrome, and Wilson disease. Nearly 2% of the couples were at risk of having offsprings with the tested autosomal recessive conditions. CONCLUSIONS: Based on the study samples, the expanded carrier screening, which specifically targeted common autosomal recessive conditions in Thai individuals, will benefit clinical outcomes, regarding preconception/prenatal genetic carrier screening.

Distribution of Epstein-Barr virus in the oral cavity of Thais with various oral mucosal conditions.

Objectives: We aimed to examine the presence of EBV, EBV strains, and variants among 3 oral conditions including normal oral mucosa (NOM), oral potentially malignant disorders/oral cancer (OPMDs/OC) and non-OPMDs/OC in a group of Thais. Material and methods: Oral exfoliated cells were obtained from 315 participants living in the northeastern and central regions of Thailand. The participants were divided into 3 groups encompassing the NOM, the OPMDs/OC and the non-OPMDs/OC groups. The presence of EBV was first determined by PCR using primers for LMP1 gene. Subsequently, EBV strains of EBNA3c and variants based on LMP1 sequences were determined by real-time PCR. Results: The prevalence of EBV in OPMDs/OC, non-OPMDs/OC and NOM were 72.0 %, 56.2 %, and 27.2 % respectively. EBV type A, B and AB were found in 52.1 %, 32.1 % and 15.8 % of all positive samples, respectively. The percentage of participants with EBV type A was more prominent in the NOM group (72.0 %) compared to the non-OPMDs/OC (54.8 %) and the OPMDs/OC group (41.8 %) whereas EBV type B was higher in the OPMDs/OC group (35.8 %) compared to the non-OPMDs/OC (31.5 %) and the NOM (24.0 %) groups. Regarding EBV variants, 30-bp deletion LMP1 variant (del-LMP1) which is more associated with malignant transformation was predominately found in the OPMDs/OC (32.8 %) and the non-OPMDs/OC (38.4 %) groups compared to the NOM group (20.0 %). Conclusions: High frequency of EBV was demonstrated in the OPMDs/OC group. EBV type A was more predominant in the NOM group whereas EBV type B was more prevalent in the OPMDs/OC group. The del-LMP1 variant was more common in the OPMDs/OC and the non-OPMDs/OC groups.

Clinical Predictive Score for Identifying Metabolic Dysfunction-Associated Steatotic Liver Disease in Individuals with Prediabetes Using Transient Elastography.

Scoring systems for metabolic dysfunction-associated steatotic liver disease (MASLD) in individuals with prediabetes have not been extensively explored. This study aimed to investigate the prevalence of MASLD and to develop predictive tools for its detection in high cardiometabolic people with prediabetes. A cross-sectional study was conducted using baseline data from the prediabetes cohort. All participants underwent transient elastography to assess liver stiffness. MASLD was defined using a controlled attenuation parameter value > 275 dB/m and/or a liver stiffness measurement ≥ 7.0 kPa. Cases with secondary causes of hepatic steatosis were excluded. Out of 400 participants, 375 were included. The observed prevalence of MASLD in individuals with prediabetes was 35.7%. The most effective predictive model included FPG ≥ 110 mg/dL; HbA1c ≥ 6.0%; sex-specific cutoffs for HDL; ALT ≥ 30 IU/L; and BMI levels. This model demonstrated good predictive performance with an AUC of 0.80 (95% CI 0.73-0.86). At a cutoff value of 4.5, the sensitivity was 70.7%, the specificity was 72.3%, the PPV was 58.8%, and the NPV was 81.5%. Our predictive model is practical, easy to use, and relies on common parameters. The scoring system should aid clinicians in determining when further investigations of MASLD are warranted among individuals with prediabetes, especially in settings with limited resources.

Genotyping Approach to Predict Coa and Cob Antigens in Thai Blood Donor Populations.

Purpose: Coa and Cob antigens of the Colton (CO) blood group system are implicated in acute and delayed hemolytic transfusion reactions (HTRs). Owing to the inadequate supply of specific antiserum, data on CO phenotypes remain limited. This study aimed to develop genotyping methods to predict Coa and Cob antigens and to estimate transfusion-induced alloimmunization risks in three Thai blood donor populations. Materials and Methods: The study included 2451 blood samples from unrelated healthy Thai blood donors obtained from central, northern, and southern Thailand. DNA sequencing was used to determine the CO*A and CO*B alleles. In-house PCR with sequence-specific primers (PCR-SSP) and high-resolution melting curve (HRM) assays were performed and genotyping results were compared using DNA sequencing. CO*A and CO*B allele frequencies among Thais were determined using PCR-SSP and their frequencies were compared with other populations. The risks of Coa and Cob transfusion-induced alloimmunization among Thai donor populations were calculated. Results: The validated genotyping results by PCR-SSP and HRM assays agreed with DNA sequencing. The CO*A/CO*A was the most common (100.0, 100.0, and 99.3%), followed by CO*A/CO*B (0.0, 0.0, and 0.7%) among central, northern and southern Thais. Homozygous CO*B/CO*B was not found. The CO*A and CO*B allele frequencies among central Thais significantly differed compared among southern Thais (p < 0.01) but not among northern Thais. Those allele frequencies among Thais were similar to those of Taiwanese, Chinese and Malay-Malaysian populations but not to South Asian, Southeast Asian, Korean, Japanese, Filipino, French Basque, and Maltese populations (p < 0.01). A higher risk of anti-Cob production rather than anti-Coa production was particularly noted in the southern Thai population. Conclusion: This study constitutes the first to determine CO*A and CO*B genotypes using PCR-SSP and HRM assays among Thais and this finding would be beneficial in predicting alloimmunization risk and providing safe transfusions among Thais.

Histopathological and risk factor analyses of oral potentially malignant disorders and oral cancer in a proactive screening in northeastern Thailand.

BACKGROUND: Lip and oral cavity cancer has been reported as the 10th most common cancer in Thailand. Recently, a screening program for oral potentially malignant disorders (OPMDs) and oral cancer was conducted in the northeastern Thailand which took into consideration a total of 371,911 people who resided in the provinces of Buriram, Chaiyaphum, Nakhon Ratchasima, and Surin. METHODS: A total of 330,914 subjects were consecutively screened for risk factors of oral cancer by village health volunteers (VHVs) using a questionnaire (S1). Then, 186,710 subjects with one or more risk factors for oral cancer were referred for oral screening by dental auxiliaries or dentists at sub-district level hospitals (S2) where 86,941 subjects were subsequently screened. Afterwards, 1576 subjects with suspicious oral lesions for OPMDs or oral cancer attended local hospitals for further investigation and treatment. Oral medicine specialists, oral surgeons, and local dentists at the district level hospitals performed biopsies and the samples were sent for histopathological analysis. The objectives of the study were to report the histopathology findings from the biopsies obtained from these subjects and the associated risk factors. RESULTS: Out of 427 subjects who received biopsies, complete diagnostic results were obtained from 409 patients (462 specimens). The 5 most common histopathological results from these specimens were mild epithelial dysplasia (27.3%), fibroepithelial hyperplasia (14.5%), oral lichen planus/oral lichenoid reactions (11.5%), moderate epithelial dysplasia (8%), and acanthosis with or without hyperkeratosis (5%). Oral squamous cell carcinoma was detected in 14 subjects and 11 other forms of oral cancer were revealed. Among the analyzed risk factors, habitual betel quid chewing was established as a statistically significant risk factor associated with OPMDs and oral cancer. CONCLUSION: The most frequently observed histopathological results of clinically suspected oral cancer and OPMDs included mild epithelial dysplasia, fibroepithelial hyperplasia, oral lichen planus/oral lichenoid reactions, moderate epithelial dysplasia, and acanthosis with or without hyperkeratosis. Betel quid chewing habit was found to be associated with OPMDs and oral cancer.

High-Resolution Melting Curve Analysis to Predict Extended Blood Group Phenotypes among Thai Donors and Patients.

Background: High-resolution melting (HRM) analysis is an alternative method for red cell genotyping. Differences in melting curves between homozygous and heterozygous genotypes can predict phenotypes in blood group systems based on single-nucleotide polymorphisms. This study aimed to implement HRM analysis to predict additional extended blood group phenotypes in Thai donor and patient populations. Methods: Blood samples obtained from 300 unrelated Thai blood donors and 23 patients with chronic transfusions were included. HRM analysis was developed and validated in genotyping of KEL*01 and KEL*02, JK*01 and JK*02, FY*01, FY*02, and FY*02 N.01, DI*01 and DI*02, GYPB*03 and GYPB*04, RHCE*E and RHCE*e, and DO*01 and DO*02. Then genotyping results from HRM and polymerase chain reaction with sequence-specific primer (PCR-SSP) and phenotyping results were compared. Results: The validated genotyping results in known DNA controls by HRM analysis agreed with DNA sequencing. The genotyping results among 300 donors in 15 alleles by HRM analysis were in complete concordance with those obtained by serological testing and PCR-SSP. The sensitivity and specificity of the HRM assay were both 100%. Among patients, 13 had alloantibodies that possessed predicted antigen-negative phenotypes corresponding to those antibody specificities, and the highest probability of genotyped-matched donors was given to the remaining patients. Conclusions: We developed and implemented the HRM analysis assay for red cell genotyping to predict extended blood group antigens in Thai donor and patient populations. The data from this study may help inform about and support transfusion care of Thai patients to reduce the risk of alloimmunisation.

Path Model Factors Associated with Depressive Symptoms among Older Thais Living in Rural Areas.

Depressive symptoms are complex and are often more severe in older people. However, there is limited research exploring the causal relationships between depression and its associated factors in the geriatric population, particularly in Thailand. We aimed to evaluate the direction of these complex relationships in the Thai population. A cross-sectional design was conducted on 312 Thai community-dwelling older adults aged 60 years or above who registered for primary care services. The participants were recruited from July 2019 to January 2020, and they responded to standard assessments. The relationships between pain, the number of medications, frailty, locomotive syndrome, and depressive symptoms were investigated using path analysis. The results showed that most participants were women and had multiple diseases, mild pain, frailty, and grade I−II locomotive syndrome. The prevalence of depressive symptoms was 16%. The model showed significant positive direct and indirect paths from locomotive syndrome to depressive symptoms (ß = 0.296, p < 0.01; ß = 0.099, p < 0.01, respectively). There was a significant positive direct path from frailty to depressive symptoms (ß = 0.219, p < 0.01) and a significant positive indirect path from pain to depressive symptoms (ß = 0.096, p < 0.01).

Sex determination using scapular and clavicular parameters in modern Thai population / Determinación del sexo utilizando parámetros escapulares y claviculares en la población tailandesa moderna

SUMMARY: As natural disasters or crimes, precise postmortem identification is needed especially in case of unknown human remains. The aim of the study is to assess sexual dimorphism by formulating new multivariate equations based on scapular and clavicular parameters for a modern Thai population. Eight left scapular and six left clavicular parameters were measured from 278 individuals (124 males and 124 females for training group; and 15 males and 15 females for test group) of a modern Thai population with age ranges from 19 to 101 years. All scapular and clavicular parameters were sexually dimorphic. Direct and stepwise multivariate discriminant function analysis was performed to generate models. Three direct multivariate discriminant functions showed accuracy rates from 91.1c to 92.3 % (cross-validated range from 90.3 % to 91.5 %). Similarly, three stepwise multivariate discriminant functions showed accuracy rates from 90.7 % to 92.7 % (cross-validated range from 90.7 % to 92.7 %). Moreover, the test group showed 86.67 % to 100 % of sex determination accuracy in six discriminant functions. As recommendation for sex determination by using combination of the scapular and clavicular parameters yields statistically high accuracy for sex determination. Therefore, the accuracies of these multivariate discriminant function equations obtained from scapula and clavicle can be applied for forensic sex determination, especially in modern Thais.

RESUMEN: En casos de desastres naturales o crímenes se requiere una identificación post mortem precisa, especialmente en el caso de restos humanos desconocidos. El objetivo de este estudio fue evaluar el dimorfismo sexual mediante nuevas ecuaciones multivariadas basadas en parámetros escapulares y claviculares para una población tailandesa moderna. Se midieron ocho parámetros escapulares izquierdos y seis claviculares izquierdos de 278 individuos (124 hombres y 124 mujeres para el grupo de entrenamiento; y 15 hombres y 15 mujeres para el grupo de prueba) de una población tailandesa moderna con rangos de edad de 19 a 101 años. Todos los parámetros escapulares y claviculares presentaban dimorfismo sexual. Se realizaron análisis de funciones discriminantes multivariadas directas paso a paso para generar modelos. Tres funciones discriminantes multivariadas directas mostraron tasas de precisión de 91,1 % a 92,3 % (rango de validación cruzada de 90,3 % a 91,5 %). De manera similar, tres funciones discriminantes multivariadas mostraron tasas de precisión de 90,7 % a 92,7 % (rango de validación cruzada de 90,7 % a 92,7 %). Además, el grupo de prueba mostró del 86,67 % al 100 % de precisión en la determinación del sexo en seis funciones discriminantes. Como recomendación para la determinación del sexo mediante el uso de la combinación de los parámetros escapulares y claviculares, se obtiene una precisión estadísticamente alta para la determinación del sexo. Por lo tanto, las precisiones de estas ecuaciones de funciones discriminantes multivariadas obtenidas de la escápula y la clavícula se pueden aplicar para la determinación forense del sexo, especialmente en los tailandeses modernos.

Development of a protein energy malnutrition screening tool for older Thais in public residential homes.

OBJECTIVE: This study aimed to develop and validate protein energy malnutrition (PEM) screening tool for older adults in public residential homes, and to test its practicality. DESIGN: This cross-sectional study consisted of two phases: tool development/validation and tool practicality evaluation. In Phase 1, the questionnaire was developed based on literature review and tested for content validity. Older residents were interviewed using this questionnaire to identify potential PEM risk factors. A 24-h recall was used to collect dietary data, and body composition and serum albumin were measured. In Phase 2, practicality of new PEM screening tool was evaluated by intended users. Data were analysed by χ2 test, Fisher's exact test, t-test, Mann-Whitney U test and multiple logistic regression. Akaike Information Criterion (AIC) was used to estimate the best fit model. SETTING: Four public residential homes in central region, Thailand. PARTICIPANTS: 249 older residents residing in public residential homes and eight intended users. RESULTS: 26·9 % had PEM (serum albumin <3·5 g/dl). According to multiple logistic regression and AIC values, PEM predictors were having pressure ulcer, experiencing significant weight loss and taking ≥ 9 types of medicine daily. These predictors were included in PEM screening tool. Regarding the tool performance test, area under the ROC curve was 0·8 (P < 0·001) with sensitivity and specificity of 83·9 and 45·5 %, respectively. For its practicality, eight intended users reported that it was useful and easy to use. CONCLUSIONS: New screening tool may be capable of identifying PEM in older residents, and further testing is required before being recommended for use.

Morphometric measurement of the proximal tibia to design the tibial component of total knee arthroplasty for the Thai population.

PURPOSE: This study evaluates the morphology of the Thai proximal tibia based on three-dimensional (3D) models to design the tibial component. METHODS: The 3D models of 480 tibias were created using reverse engineering techniques from computed tomography imaging data obtained from 240 volunteers (120 males, 120 females; range 20-50 years). Based on 3D measurements, a digital ruler was used to measure the distance between the triangular points of the models. The morphometric parameters consisted of mediolateral length (ML), anteroposterior width (AP), medial anteroposterior width (MAP), lateral anteroposterior width (LAP), central to a medial length (CM), central to a lateral length (CL), medial anterior radius (MAR), lateral anterior radius (LAR), and tibial aspect ratio (AR). An independent t-test was performed for gender differences, and K-means clustering was used to find the optimum sizes of the tibial component with a correlation between ML length and AP width in Thai people. RESULTS: The average morphometric parameters of Thai proximal tibia, namely ML, AP, MAP, LAP, CM, and CL, were as follows: 72.52 ± 5.94 mm, 46.36 ± 3.84 mm, 49.22 ± 3.62 mm, 43.59 ± 4.05 mm, 14.29 ± 2.72 mm, and 15.28 ± 2.99 mm, respectively. The average of MAR, LAR, and AR was 24.43 ± 2.11 mm, 21.52 ± 2.00 mm, and 1.57 ± 0.08, respectively. All morphometric parameters in males were significantly higher than those of females. There was a difference between the Thai proximal tibia and other nationalities and a mismatch between the size of the commercial tibial component and the Thai knee. Using K-means clustering analysis, the recommended number of ML and AP is seven sizes for the practical design of tibial components to cover the Thai anatomy. CONCLUSION: The design of the tibial component should be recommended to cover the anatomy of the Thai population. These data provide essential information for the specific design of Thai knee prostheses.

Anatomic position of the asterion and implication for neurosurgical procedure / Posición anatómica del asterion y sus implicancias en el procedimiento neuroquirúrgico

SUMMARY: The asterion is the joining of the lambdoid, parietomastoid, and occipitomastoid sutures. It is classified into two types, type I shows small bones or woven bones, while in type II, woven bones are non-existent. In this study, forty cadavers were conducted and observed the asterion on both sides of skulls showing the approximate ratio of type II and type I was 3:2. The asterion was located by measuring the distances from the asterion to skull landmarks, including inion, the root of zygoma, and mastoid tip. The mean distance between asterion and inion was 62.9 ? 6.0 mm. The mean distance between asterion and the root of zygomatic arch was 58.3 ? 6.1 mm, whereas the mean distance between asterion and mastoid tip was 51.1 ? 5.3 mm. The most common location related to the asterion was the dural venous sinuses on 65 % of tested sides, followed by infratentorial dura and supratentorial dura (25 % and 10 %, respectively). However, the authors found no differences between sexes, sides, and types in any underlying structures.

RESUMEN: El asterion es la unión de las suturas lambdoidea, parietomastoidea y occipitomastoidea. Clasificado en dos tipos, el tipo I muestra huesos pequeños o hueso laminar, mientras que en el tipo II, el hueso laminar es inexistente. En este trabajo se estudiaron 40 cadáveres y se observó el asterion en ambos lados de los cráneos correspondientes, mostrando una proporción aproximada de tipo II y tipo I de 3:2. El asterion se localizó midiendo las distancias asociadas a puntos de referencia del cráneo: el inion, la raíz del arco cigomático y el ápice del proceso mastoides. La distancia media entre el asterion y el inion fue de 62,9 ? 6,0 mm. La distancia media entre el asterion y la raíz del arco cigomático fue de 58,3 ? 6,1 mm, mientras que la distancia media entre el asterion y el ápice del proceso mastoides fue de 51,1 ? 5,3 mm. La localización más común relacionada con el asterion fueron los senos venosos durales en el 65 % de los lados evaluados, seguido de la duramadre infratentorial y la dura supratentorial (25 % y 10 %, respectivamente). Sin embargo, los autores no encontraron diferencias entre sexo, lados y tipo en ninguna estructura subyacente.

HLA-B*13 :01 Is a Predictive Marker of Dapsone-Induced Severe Cutaneous Adverse Reactions in Thai Patients.

HLA-B*13:01 allele has been identified as the genetic determinant of dapsone hypersensitivity syndrome (DHS) among leprosy and non-leprosy patients in several studies. Dapsone hydroxylamine (DDS-NHOH), an active metabolite of dapsone, has been believed to be responsible for DHS. However, studies have not highlighted the importance of other genetic polymorphisms in dapsone-induced severe cutaneous adverse reactions (SCAR). We investigated the association of HLA alleles and cytochrome P450 (CYP) alleles with dapsone-induced SCAR in Thai non-leprosy patients. A prospective cohort study, 16 Thai patients of dapsone-induced SCARs (5 SJS-TEN and 11 DRESS) and 9 Taiwanese patients of dapsone-induced SCARs (2 SJS-TEN and 7 DRESS), 40 dapsone-tolerant controls, and 470 general Thai population were enrolled. HLA class I and II alleles were genotyped using polymerase chain reaction-sequence specific oligonucleotides (PCR-SSOs). CYP2C9, CYP2C19, and CYP3A4 genotypes were determined by the TaqMan real-time PCR assay. We performed computational analyses of dapsone and DDS-NHOH interacting with HLA-B*13:01 and HLA-B*13:02 alleles by the molecular docking approach. Among all the HLA alleles, only HLA-B*13:01 allele was found to be significantly associated with dapsone-induced SCARs (OR = 39.00, 95% CI = 7.67-198.21, p = 5.3447 × 10-7), SJS-TEN (OR = 36.00, 95% CI = 3.19-405.89, p = 2.1657 × 10-3), and DRESS (OR = 40.50, 95% CI = 6.38-257.03, p = 1.0784 × 10-5) as compared to dapsone-tolerant controls. Also, HLA-B*13:01 allele was strongly associated with dapsone-induced SCARs in Asians (OR = 36.00, 95% CI = 8.67-149.52, p = 2.8068 × 10-7) and Taiwanese (OR = 31.50, 95% CI = 4.80-206.56, p = 2.5519 × 10-3). Furthermore, dapsone and DDS-NHOH fit within the extra-deep sub pocket of the antigen-binding site of the HLA-B*13:01 allele and change the antigen-recognition site. However, there was no significant association between genetic polymorphism of cytochrome P450 (CYP2C9, CYP2C19, and CYP3A4) and dapsone-induced SCARs (SJS-TEN and DRESS). The results of this study support the specific genotyping of the HLA-B*13:01 allele to avoid dapsone-induced SCARs including SJS-TEN and DRESS before initiating dapsone therapy in the Asian population.

Ala97Ser transthyretin amyloidosis-associated polyneuropathy, clinical and neurophysiological profiles in a Thai cohort.

BACKGROUND: Ala97Ser transthyretin amyloidosis-associated polyneuropathy (ATTRA97S-PN) is a rare form of inherited polyneuropathy, usually manifesting with late-onset (> 50) progressive polyneuropathy. This mutation is mostly prevalent in Taiwanese and Han-Chinese individuals. The aim of this study was to describe the clinical and comprehensive neurophysiological profiles of ATTRA97S-PN in Thai patients. METHODS: The clinical profiles and serial neurophysiologic studies (nerve conduction study (NCS), quantitative sensory test (QST), and comprehensive autonomic function test (AFT)) of symptomatic ATTRA97S-PN patients who had been followed-up at King Chulalongkorn Memorial Hospital during 2010-2020 were retrospectively reviewed. RESULTS: Nine symptomatic patients (55.6 % were male) from four unrelated families were included. All were Thais of mixed Thai Chinese descent. The mean age of onset was 48.3 (32-60) years. The mean age at diagnosis was 54.8 (33-66) years. Three patients developed early-onset (< 40y) polyneuropathy. The mean Neuropathy Impairment Score was 41.33 (10-92) at diagnosis. Sensory (9/9) and autonomic (9/9) neuropathies were more frequent than motor neuropathy (5/9), which appeared in the late stage of disease. Hypoesthesia in the feet, and gastrointestinal autonomic symptoms were frequently reported as the initial symptoms. The course of neuropathy progressed over years to decades. The worsening of neuropathy tended to progress faster once motor nerves were affected in both clinical and neurophysiological aspects. Concurrent cardiac amyloidosis was found in 6/9 patients. NCS showed length-dependent sensorimotor axonal polyneuropathy in 5/9 patients, and median neuropathy at the wrist (mostly bilateral) in 7/9 patients. QST showed abnormalities in the vibratory detection threshold, the cold detection threshold and the heat pain sensation in 8/9, 8/9 and 7/7 tested patients, respectively. AFT results were abnormal in all. The mean composite autonomic severity score was 5 (3-9). CONCLUSIONS: This clinical study is the first of ATTRA97S-PN in Thai patients. The mixed polyneuropathy-cardiopathy phenotype was the most common manifestation. In this cohort, the age of onset was lower, and the course of neuropathy was relatively longer, than that in previous studies. Some patients may develop early-onset polyneuropathy. This mutation has not yet been documented in any population other than Han Chinese-related populations, probably suggesting a founder effect. Further studies are warranted.

Anti-HBV Activities of Polysaccharides from Thais clavigera (Küster) by In Vitro and In Vivo Study.

Hepatitis B virus (HBV) infection remains a major global health problem. It is therefore imperative to develop drugs for anti-hepatitis B with high-efficiency and low toxicity. Attracted by the observations and evidence that the symptoms of some patients from the Southern Fujian, China, suffering from hepatitis B were alleviated after daily eating an edible marine mollusk, Thais clavigera (Küster 1860) (TCK). Water-soluble polysaccharide from TCK (TCKP1) was isolated and characterized. The anti-HBV activity of TCKP1 and its regulatory pathway were investigated on both HepG2.2.15 cell line and HBV transgenic mice. The data obtained from in vitro studies showed that TCKP1 significantly enhanced the production of IFN-α, and reduced the level of HBV antigens and HBV DNA in the supernatants of HepG2.2.15 cells in a dose-dependent manner with low cytotoxicity. The result of the study on the HBV transgenic mice further revealed that TCKP1 significantly decreased the level of transaminases, HBsAg, HBeAg, and HBV DNA in the serum, as well as HBsAg, HBeAg, HBV DNA, and HBV RNA in the liver of HBV transgenic (HBV-Tg) mice. Furthermore, TCKP1 exhibited equivalent inhibitory effect with the positive control tenofovir alafenamide (TAF) on the markers above except for HBV DNA even in low dosage in a mouse model. However, the TCKP1 high-dose group displayed stronger inhibition of transaminases and liver HBsAg, HBeAg, and HBV RNA when compared with those of TAF. Meanwhile, inflammation of the liver was, by pathological observation, relieved in a dose-dependent manner after being treated with TCKP1. In addition, elevated levels of interleukin-12 (IL-12) and interferon γ (IFN-γ), and reduced level of interleukin-4 (IL-4) in the serum were observed, indicating that the anti-HBV effect of TCKP1 was achieved by potentiating immunocyte function and regulating the balance of Th1/Th2 cytokines.

Major Histocompatibility Complex Class I Chain-Related A and B (MICA and MICB) Gene, Allele, and Haplotype Associations With Dengue Infections in Ethnic Thais.

BACKGROUND: Major histocompatibility complex class I chain-related (MIC) A and B (MICA and MICB) are polymorphic stress molecules recognized by natural killer cells. This study was performed to analyze MIC gene profiles in hospitalized Thai children with acute dengue illness. METHODS: MIC allele profiles were determined in a discovery cohort of patients with dengue fever or dengue hemorrhagic fever (DHF) (n = 166) and controls (n = 149). A replication cohort of patients with dengue (n = 222) was used to confirm specific MICB associations with disease. RESULTS: MICA*045 and MICB*004 associated with susceptibility to DHF in secondary dengue virus (DENV) infections (odds ratio [OR], 3.22; [95% confidence interval (CI), 1.18-8.84] and 1.99 [1.07-2.13], respectively), and MICB*002 with protection from DHF in secondary DENV infections (OR, 0.41; 95% CI, .21-.68). The protective effect of MICB*002 against secondary DHF was confirmed in the replication cohort (OR, 0.43; 95% CI, .22-.82) and was stronger when MICB*002 is present in individuals also carrying HLA-B*18, B*40, and B*44 alleles which form the B44 supertype of functionally related alleles (0.29, 95% CI, .14-.60). CONCLUSIONS: Given that MICB*002 is a low expresser of soluble proteins, these data indicate that surface expression of MICB*002 with B44 supertype alleles on DENV-infected cells confer a protective advantage in controlling DENV infection using natural killer cells.

Impact of using genotyping to predict SERF negative phenotype in Thai blood donor populations.

BACKGROUND: SERF(+) is a high prevalence antigen in the Cromer blood group system that is encoded by a CROM*01.12 allele. The SERF(-) on red cells is caused by a single nucleotide variation, c.647C＞T, in exon 5 of the Decay-accelerating factor, DAF gene. Alloanti-SERF was found in a pregnant Thai woman, and a SERF(-) individual was found among Thai blood donors. Since anti-SERF is commercially unavailable, this study aimed to develop appropriate genotyping methods for CROM*01.12 and CROM*01.-12 alleles and predict the SERF(-) phenotype in Thai blood donors. METHODS: DNA samples obtained from 1,580 central, 300 northern, and 427 southern Thai blood donors were genotyped for CROM*01.12 and CROM*01.-12 allele detection using in-house PCR with sequence-specific primer (PCR-SSP) confirmed by DNA sequencing. RESULTS: Validity of the PCR-SSP genotyping results agreed with DNA sequencing; CROM*01.12/ CROM*01.12 was the most common (98.42%, 98.00%, and 98.59%), followed by CROM*01.12/CROM*01.-12 (1.58%, 2.00%, and 1.41%) among central, northern, and southern Thais, respectively. CROM*01.-12/CROM*01.-12 was not detected in all three populations. The alleles found in central Thais did not significantly differ from those found in northern and southern Thais. CONCLUSION: This study is the first to distinguish the predicted SERF phenotypes from genotyping results obtained using in-house PCR-SSP, confirming that the CROM*01.-12 allele frequency ranged from 0.007 to 0.010 in three Thai populations. This helps identify the SERF(-) phenotype among donors and patients, ultimately preventing adverse transfusion reactions.

A novel nonsense mutation found in the CD177 gene of Thai individuals with the HNA-2 null phenotype.

OBJECTIVES: The aim of this study is to explore the molecular basis and to develop a simple sequence-specific primer polymerase chain reaction (PCR-SSP) technique for screening genotypes associated with the human neutrophil antigen-2 (HNA-2) null phenotype among Thai blood donors. BACKGROUND: Single-nucleotide polymorphisms (SNPs) c.787A>T of the CD177 gene is well known to be primarily demonstrated as a genetic determinant for HNA-2 deficiency. METHODS: The SNPs in the CD177 gene (exons 7 and 9) of 49 Thai blood donors with the known percentage of CD177 expression by flow cytometry including 48 HNA-2 positive and 1 HNA-2 null individuals were identified by long-range PCR amplification and sequencing. Moreover, screening for the c.1254G>A mutation was developed using an in-house PCR-SSP technique and tested among 771 unrelated donor samples. RESULTS: A HNA-2 null sample from the first cohort was heterozygous for c.787A/T and homozygous for c.1291G/G, namely, a 787A-1291G/787T-1291G (AG/TG) genotype. Interestingly, we could identify SNP c.1254G>A (rs188387562, p. Trp418Ter) that caused a nonsense mutation of the CD177 gene in exon 9. This individual might have the 787A-1254A-1291G/787T-1254G-1291G genotype. From the second cohort (771 unrelated donors), the 1254GG homozygote was the most common (96.37%), followed by the 1254GA heterozygote (3.50%) and 1254AA homozygote (0.13%). Blood samples of two individuals with 787AT-1254GA-1291GG and 787AA-1254AA-1291GG genotypes were tested and the HNA-2 antigen expressions were 0.03% and 0.16% in rank. CONCLUSIONS: The c.787A>T is a primary genetic hallmark to determine the HNA-2 null phenotype. Additional screening of the novel c.1254G>A in combination with c.787A>T is a suitable, convenient and effective diagnosis among Thais.

Genomewide Association Study Confirming the Association of NAT2 with Susceptibility to Antituberculosis Drug-Induced Liver Injury in Thai Patients.

Antituberculosis drug-induced liver injury (ATDILI) is a common side effect leading to tuberculosis (TB) treatment disruption. The mechanism of the disease remains poorly understood. We conducted a genomewide association study (GWAS) to investigate all possible genetic factors of ATDILI in Thai patients. This study was carried out in Thai TB patients, including 79 ATDILI cases and 239 tolerant controls from our network hospitals in Thailand. Nearly 1 million single-nucleotide polymorphisms (SNPs) were genotyped across the whole genome using an Illumina OmniExpress Exome BeadChip array. In the discovery stage, we identified strong association signals on chromosome 8 originating from the N-acetyltransferase (NAT2) region. The A allele of rs1495741, the top SNP in the intergenic region of NAT2 and PSD3 (14 kb from NAT2), was significantly associated with ATDILI (recessive model, odds ratio of 6.01 [95% confidence interval, 3.42 to 10.57]; P = 6.86E-11). This particular SNP was reported as a tag SNP for NAT2 inferred phenotypes. The AA, AG, and GG genotypes represented NAT2 slow acetylators, intermediate acetylators, and fast acetylators, respectively. The tag SNP genotypes demonstrated a concordance rate of 94.98% with NAT2 acetylator phenotypes. This GWAS shows that NAT2 is the most important risk factor for ATDILI in the Thai population.