Biomedical subjects

Marie Lin

Publications and source records attributed to Marie Lin.

17 recordsLinked to original sources

PubMed2006

Genetic variations of HLA-DRB1 and susceptibility to Kawasaki disease in Taiwanese children.

Although some previous studies have reported that genetic and immunologic factors play important roles in the pathogenesis of Kawasaki disease (KD), the etiologic factors of this enigmatic pediatric disease are still poorly understood. The purpose of this study was to investigate whether polymorphisms of the human leukocyte antigen DRB1 (HLA-DRB1) gene are associated with KD and the development of coronary artery lesions (CAL) in Taiwanese children. Genomic DNA was extracted from whole blood samples from 145 children with KD and 331 healthy controls. The HLA-DRB1 gene was genotyped by polymerase chain reaction (PCR) and sequence-based typing assays. We found that the distribution of HLA-DRB1 allele families and alleles in children with KD did not differ from that in healthy controls. Stratified analysis did not demonstrate any association between particular HLA-DRB1 allele families or alleles and the development of CAL in children with KD. These findings suggest that susceptibility to KD and CAL is not associated with the HLA-DRB1 gene in a Taiwanese population. If immunogenetic determinants are involved in this disease and its complications in Taiwanese children, they must involve genes other than HLA-DRB1.

Child↗

PubMed2006

HLA-DRB1 alleles and cervical squamous cell carcinoma: experimental study and meta-analysis.

Polymorphisms in human leukocyte antigen (HLA) genes have been implicated in the risk for cervical cancer. Association of certain class II HLA alleles with cervical cancer has been documented in various ethnic populations. The implications of such an association, however, are controversial. We analyzed 126 Chinese women with cervical squamous cell carcinoma (CSCC) and 289 healthy controls to test associations of certain HLA-DRB1 alleles. We then performed meta-analyses combining our own experimental data and data from nine other published studies. We found no significant differences in HLA-DRB1 allele frequencies in both CSCC and HPV-16-positive CSCC patients and control subjects. Meta-analysis provided evidence that four allele families (HLA-DRB1*04, *07, *11, and *15) and seven alleles (HLA-DRB1*0403, *0405, *0407, *0701, *1501, *1502, and *1503) were positively associated and two allele families (HLA-DRB1*09 and *13) and four alleles (HLA-DRB1*0901, *1301, *1302, and *1602) were negatively associated with CSCC in all studies or in Caucasian subgroups. In conclusion, our meta-analysis confirms the apparent association between certain HLA-DRB1 allele families and alleles and CSCC, suggesting that oncogenesis in this disease may be related to defects in immunoregulation. Larger studies may be needed, particularly in various ethnic groups, to further substantiate these associations.

Adult↗

PubMed2006

Taiwan experience suggests that RhD typing for blood transfusion is unnecessary in southeast Asian populations.

BACKGROUND: The high frequency of RhD (D) antigen among Taiwanese persons (99.67%) often imposes unnecessary risks of under-transfusion on D- patients awaiting D- blood. Also because of the rare occurrence of anti-D among Taiwanese persons, routine pretransfusion D typing has been discontinued in the Mackay Memorial Hospital since 1988. This report is the retrospective evaluation of the outcome of abolishing RhD typing for Taiwanese. STUDY DESIGN AND METHODS: More than 10 years of alloantibody data at Mackay Memorial Hospital Blood Bank were reviewed. The cases with anti-D were further used to analyze the potency of D antigen and to observe whether there were differences in the incidence of anti-D before and after discontinuation of routine D typing among Taiwanese individuals. RESULTS: The incidence of anti-D before and after discontinuation of routine pretransfusion D typing has remained unchanged. The immunogenicity of D and "Mi(a)" in Taiwanese persons is found to be similar. In terms of opportunity for immunization, however, the "Mi(a)" antigen (phenotype frequency 7.3% in Taiwanese persons) has become the most important blood group antigen in Taiwan. CONCLUSION: The results strongly support the exclusion of D typing from routine compatibility testing for individuals of Taiwanese origin. Because the low incidence of D- and relatively high incidence of "Mi(a)"+ phenotypes are common findings throughout southeast Asia, and because a population genetic study revealed that the Taiwanese people are genetically related to southern Asian populations, it is suggested that RhD typing for blood transfusion is unnecessary among southeast Asian populations.

Asian People↗

PubMed2006

A novel IGnT allele responsible for the adult i phenotype.

BACKGROUND: The adult i phenotype has been characterized as the presence of a very low level of I antigen but a high quantity of I antigen on red blood cells (RBCs). It has been noted that this rare phenotype is partially associated with congenital cataracts. It has been demonstrated that the human I locus expresses three IGnT forms, IGnTA, IGnTB, and IGnTC, and that the IGnTC gene is responsible for the I antigen expression on RBCs. This report describes molecular genetic analysis of a Taiwanese person with the adult i phenotype but without congenital cataracts. STUDY DESIGN AND METHODS: The five exon regions of the IGnT gene of the adult i individual were amplified by polymerase chain reaction (PCR) and cloned, and the sequences were determined. The activity of the IGnT enzyme expressed from the mutant IGnTC gene identified in this i adult was analyzed. RESULTS: The presented adult i individual possesses wild-type IGnTA and IGnTB genes but a mutant IGnTC gene with a 243T>A nucleotide substitution, which predicts an amino acid alteration of Asn81Lys. PCR-restriction fragment length polymorphism analysis has been used to show that this IGnTC*243A allele is uncommon in the general Taiwanese population. The activity of the IGnT enzyme expressed from the mutant IGnTC*243A gene was significantly reduced when compared with that expressed from the wild-type IGnTC gene. CONCLUSION: A novel IGnTC allele with a 243T>A missense mutation was demonstrated in our adult i Taiwanese without congenital cataracts. The molecular basis revealed for this adult i case agrees with the proposed molecular genetic mechanism, accounting for the partial association of the adult i phenotype with congenital cataracts.

Adult↗

PubMed2005

Functional interactions of Raf and MEK with Jun-N-terminal kinase (JNK) result in a positive feedback loop on the oncogenic Ras signaling pathway.

In previous studies we have found that oncogenic (Val 12)-ras-p21 induces Xenopus laevis oocyte maturation that is selectively blocked by two ras-p21 peptides, 35-47, also called PNC-7, that blocks its interaction with raf, and 96-110, also called PNC-2, that blocks its interaction with jun-N-terminal kinase (JNK). Each peptide blocks activation of both JNK and MAP kinase (MAPK or ERK) suggesting interaction between the raf-MEK-ERK and JNK-jun pathways. We further found that dominant negative raf blocks JNK induction of oocyte maturation, again suggesting cross-talk between pathways. In this study, we have undertaken to determine where these points of cross-talk occur. First, we have immunoprecipitated injected Val 12-Ha-ras-p21 from oocytes and found that a complex forms between ras-p21 raf, MEK, MAPK, and JNK. Co-injection of either peptide, but not a control peptide, causes diminished binding of ras-p21, raf, and JNK. Thus, one site of interaction is cooperative binding of Val 12-ras-p21 to raf and JNK. Second, we have injected JNK, c-raf, and MEK into oocytes alone and in the presence of raf and MEK inhibitors and found that JNK activation is independent of the raf-MEK-MAPK pathway but that activated JNK activates raf, allowing for activation of ERK. Furthermore, we have found that constitutively activated MEK activates JNK. We have corroborated these findings in studies with isolated protein components from a human astrocyte (U-251) cell line; that is, JNK phosphorylates raf but not the reverse; MEK phosphorylates JNK but not the reverse. We further have found that JNK does not phosphorylate MAPK and that MAPK does not phosphorylate JNK. The stress-inducing agent, anisomycin, causes activation of JNK, raf, MEK, and ERK in this cell line; activation of JNK is not inhibitable by the MEK inhibitor, U0126, while activation of raf, MEK, and ERK are blocked by this agent. These results suggest that activated JNK can, in turn, activate not only jun but also raf that, in turn, activates MEK that can then cross-activate JNK in a positive feedback loop.

Animals↗

PubMed2005

Traces of archaic mitochondrial lineages persist in Austronesian-speaking Formosan populations.

Genetic affinities between aboriginal Taiwanese and populations from Oceania and Southeast Asia have previously been explored through analyses of mitochondrial DNA (mtDNA), Y chromosomal DNA, and human leukocyte antigen loci. Recent genetic studies have supported the "slow boat" and "entangled bank" models according to which the Polynesian migration can be seen as an expansion from Melanesia without any major direct genetic thread leading back to its initiation from Taiwan. We assessed mtDNA variation in 640 individuals from nine tribes of the central mountain ranges and east coast regions of Taiwan. In contrast to the Han populations, the tribes showed a low frequency of haplogroups D4 and G, and an absence of haplogroups A, C, Z, M9, and M10. Also, more than 85% of the maternal lineages were nested within haplogroups B4, B5a, F1a, F3b, E, and M7. Although indicating a common origin of the populations of insular Southeast Asia and Oceania, most mtDNA lineages in Taiwanese aboriginal populations are grouped separately from those found in China and the Taiwan general (Han) population, suggesting a prevalence in the Taiwanese aboriginal gene pool of its initial late Pleistocene settlers. Interestingly, from complete mtDNA sequencing information, most B4a lineages were associated with three coding region substitutions, defining a new subclade, B4a1a, that endorses the origin of Polynesian migration from Taiwan. Coalescence times of B4a1a were 13.2 +/- 3.8 thousand years (or 9.3 +/- 2.5 thousand years in Papuans and Polynesians). Considering the lack of a common specific Y chromosomal element shared by the Taiwanese aboriginals and Polynesians, the mtDNA evidence provided here is also consistent with the suggestion that the proto-Oceanic societies would have been mainly matrilocal.

Asian People↗

PubMed2005

HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol.

Allopurinol, a commonly prescribed medication for gout and hyperuricemia, is a frequent cause of severe cutaneous adverse reactions (SCAR), which include the drug hypersensitivity syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The adverse events are unpredictable and carry significant morbidity and mortality. To identify genetic markers for allopurinol-SCAR, we carried out a case-control association study. We enrolled 51 patients with allopurinol-SCAR and 228 control individuals (135 allopurinol-tolerant subjects and 93 healthy subjects from the general population), and genotyped for 823 SNPs in genes related to drug metabolism and immune response. The initial screen revealed strong association between allopurinol-SCAR and SNPs in the MHC region, including BAT3 (encoding HLA-B associated transcript 3), MSH5 (mutS homolog 5), and MICB (MHC class I polypeptide-related sequence B) (P < 10(-7)). We then determined the alleles of HLA loci A, B, C, and DRB1. The HLA-B*5801 allele was present in all (100%) 51 patients with allopurinol-SCAR, but only in 20 (15%) of 135 tolerant patients [odds ratio 580.3 (95% confidence interval, 34.4-9780.9); corrected P value = 4.7 x 10(-24)] and in 19 (20%) of 93 of healthy subjects [393.51 (23.23-6665.26); corrected P value = 8.1 x 10(-18)]. HLA alleles A*3303, Cw*0302, and DRB1*0301 were in linkage disequilibrium and formed an extended haplotype with HLA-B*5801. Our results indicated that allopurinol-SCAR is strongly associated with a genetic predisposition in Han Chinese. In particular, HLA-B*5801 allele is an important genetic risk factor for this life-threatening condition.

Aged↗

PubMed2005

A novel A allele with 664G>A mutation identified in a family with the Am phenotype.

BACKGROUND: The Am phenotype has been characterized as a weak expression of the A antigen on red blood cells but the presence of a normal quantity of the A antigen in saliva. This study describes a molecular genetic analysis of members of an Am family. STUDY DESIGN AND METHODS: The eight exon regions of the ABO genes of the Am proposita were amplified by polymerase chain reaction and cloned, and their sequences were analyzed. The alpha-1,3-N-acetylgalactosaminyltransferase (A-transferase) activities of the Am serum and the expressed Am transferase were analyzed. RESULTS: An A gene with a 664G>A mutation, which predicts an amino acid alteration of Val222Met, was identified in the Am proposita. This Am664A allele was demonstrated in other three family members with the Am phenotype. The A-transferase activity was virtually undetectable in the Am sera, and the expressed Am transferase showed weak A-transferase activity, when compared with the expressed A1 transferase, in assays that use acceptor substrates mimicking the Type 2 H structure and Type 1 H structure. CONCLUSION: A novel A allele with 664G>A mutation was demonstrated in a pedigree with the Am phenotype. The mechanism leading to the formation of the Am phenotype still awaits elucidation.

ABO Blood-Group System↗

PubMed2005

The CBLB gene and Graves' disease in children.

The CBLB gene functions as a negative regulator of autoimmunity. Impairment of the Cbl-b signaling pathway may contribute to human autoimmune disease. dbSNP rs2305035 is a C/T polymorphism located in exon 10 of the CBLB gene. We report an association study of this polymorphism in children with Graves' disease. The patients were 158 unrelated children (125 girls) with Graves' disease, aged 9.8 +/- 3.3 years. The controls consisted of 237 adults without a history of autoimmune disease. The C allele and phenotype frequencies of patients and controls were 247 (78.2%) vs 356 (75.1%) (OR = 1.19, p >0.05) and 151 (95.6%) vs 221 (93.2%) (OR = 1.56, p >0.05), respectively. The allelic polymorphism in patients and controls with and without DRB1*09012 were also not significantly different. This study demonstrates that the C/T polymorphism in exon 10 of the CBLB gene is not associated with Graves' disease in children.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Filtering of ineffective siRNAs and improved siRNA design tool.

MOTIVATION: Short interfering RNAs (siRNAs) can be used to suppress gene expression and possess many potential applications in therapy, but how to design an effective siRNA is still not clear. Based on the MPI (Max-Planck-Institute) basic principles, a number of siRNA design tools have been developed recently. The set of candidates reported by these tools is usually large and often contains ineffective siRNAs. In view of this, we initiate the study of filtering ineffective siRNAs. RESULTS: The contribution of this paper is 2-fold. First, we propose a fair scheme to compare existing design tools based on real data in the literature. Second, we attempt to improve the MPI principles and existing tools by an algorithm that can filter ineffective siRNAs. The algorithm is based on some new observations on the secondary structure, which we have verified by AI techniques (decision trees and support vector machines). We have tested our algorithm together with the MPI principles and the existing tools. The results show that our filtering algorithm is effective. AVAILABILITY: The siRNA design software tool can be found in the website http://www.cs.hku.hk/~sirna/ CONTACT: smyiu@cs.hku.hk

Algorithms↗

PubMed2004

Compatibility testing without a centrifuge: the slide Polybrene method.

BACKGROUND: A simple and rapid slide Polybrene method (SP) for pretransfusion compatibility testing is described. SP is particularly suitable for use in developing countries where, due to limited resources, centrifuges and biologic reagents may not be readily available. STUDY DESIGN AND METHODS: The original manual Polybrene method (MP) was modified for use on glass microscope slides, eliminating the need for test tubes and centrifugation. The sensitivity of SP for detecting alloantibodies to RBC antigens was compared with that of MP and the IAT. RESULTS: Both SP and MP were more sensitive than the IAT for detecting anti-E. SP detected 21 of 23 examples of anti'-Mi(a)' and 7 of 8 examples of anti-E. Kidd and Diego system antibodies were also readily detectable by SP, although the reactions were weaker than those observed with both MP and IAT. However, both SP and MP failed to detect some examples of antibodies to Kell system antigens. CONCLUSIONS: SP is an acceptable method for compatibility testing in developing countries, particularly in populations where the frequency of K is low (e.g., southeast Asia). The reagents are inexpensive and can be prepared in-house. SP is simple to use, does not require a centrifuge, and can be performed by personnel with minimal training.

Antibodies↗

PubMed2003

Association of HLA class I with severe acute respiratory syndrome coronavirus infection.

BACKGROUND: The human leukocyte antigen (HLA) system is widely used as a strategy in the search for the etiology of infectious diseases and autoimmune disorders. During the Taiwan epidemic of severe acute respiratory syndrome (SARS), many health care workers were infected. In an effort to establish a screening program for high risk personal, the distribution of HLA class I and II alleles in case and control groups was examined for the presence of an association to a genetic susceptibly or resistance to SARS coronavirus infection. METHODS: HLA-class I and II allele typing by PCR-SSOP was performed on 37 cases of probable SARS, 28 fever patients excluded later as probable SARS, and 101 non-infected health care workers who were exposed or possibly exposed to SARS coronavirus. An additional control set of 190 normal healthy unrelated Taiwanese was also used in the analysis. RESULTS: Woolf and Haldane Odds ratio (OR) and corrected P-value (Pc) obtained from two tails Fisher exact test were used to show susceptibility of HLA class I or class II alleles with coronavirus infection. At first, when analyzing infected SARS patients and high risk health care workers groups, HLA-B*4601 (OR = 2.08, P = 0.04, Pc = n.s.) and HLA-B*5401 (OR = 5.44, P = 0.02, Pc = n.s.) appeared as the most probable elements that may be favoring SARS coronavirus infection. After selecting only a "severe cases" patient group from the infected "probable SARS" patient group and comparing them with the high risk health care workers group, the severity of SARS was shown to be significantly associated with HLA-B*4601 (P = 0.0008 or Pc = 0.0279). CONCLUSIONS: Densely populated regions with genetically related southern Asian populations appear to be more affected by the spreading of SARS infection. Up until recently, no probable SARS patients were reported among Taiwan indigenous peoples who are genetically distinct from the Taiwanese general population, have no HLA-B* 4601 and have high frequency of HLA-B* 1301. While increase of HLA-B* 4601 allele frequency was observed in the "Probable SARS infected" patient group, a further significant increase of the allele was seen in the "Severe cases" patient group. These results appeared to indicate association of HLA-B* 4601 with the severity of SARS infection in Asian populations. Independent studies are needed to test these results.

Adult↗

PubMed2003

Molecular genetic analysis for the Ae1 and A3 alleles.

BACKGROUND: In addition to the common ABO phenotypes, numerous phenotypes with a weak expression of the A or B antigens on RBCs have been found. This study describes the molecular genetic analysis of the Ael and the A3 phenotypes. STUDY DESIGN AND METHODS: The seven-exon regions of the ABO genes of Ael and A3B individuals were amplified by PCR and cloned, and the sequences of the exons and their adjacent splice sites were analyzed. Samples from 30 randomly selected A1 individuals were also assessed. RESULTS: The A gene with wild-type coding sequence was demonstrated in the Ael propositus, but all the six unrelated Taiwanese people with the Ael or AelB phenotype were shown to possess an A allele with the G-->A mutation at the +5 position of intron 6 (IVS6+5G-->A). RT-PCR analysis showed that the complete A transcript structure was absent in the Ael RNA samples. The A3B individual possessed an A gene with an 838C-->T missense mutation. CONCLUSION: The results suggest an association of the Ael*IVS6+5G-->A allele with the Ael phenotype in Taiwanese people. The mechanism defining how the Ael*IVS6+5G-->A allele leads to the Ael phenotype awaits elucidation.

ABO Blood-Group System↗

PubMed2002

The molecular genetics of the human I locus and molecular background explain the partial association of the adult i phenotype with congenital cataracts.

The human i and I antigens are characterized as linear and branched repeats of N-acetyllactosamine, respectively. Conversion of the i to the I structure requires I-branching beta-1,6-N-acetylglucosaminyltransferase activity. It has been noted that the null phenotype of I, the adult i phenotype, is associated with congenital cataracts in Asians. Previously, the identification of molecular changes in the IGnT gene, associated with the adult i phenotype, has been reported. In the present study, we demonstrate that the human I locus expresses 3 IGnT forms, designated IGnTA, IGnTB, and IGnTC, which have different exon 1, but identical exons 2 and 3, coding regions. The molecular genetics proposed for the I locus offer a new perspective on the formation and expression of the I antigen in different cells and provide insight into the questions derived from investigation of the adult i phenotype. Molecular genetic analyses of the I loci of the 2 adult i groups, with and without congenital cataracts, were performed, and enzyme function assays and expression patterns for the 3 IGnT transcripts in reticulocytes and lens-epithelium cells were analyzed. The results suggest a molecular genetic mechanism that may explain the partial association of the adult i phenotype with congenital cataracts and indicate that a defect in the I locus may lead directly to the development of congenital cataracts. The results also suggest that the human blood group I gene should be reassigned to the IGnTC form, not the IGnTB form, as described previously.

Adult↗

PubMed2002

Molecular genetic analysis for the B(3) allele.

Molecular genetic analysis of 14 samples from unrelated individuals with the B(3) phenotype is reported here. Two different molecular changes in the blood group B gene were observed. One case was demonstrated to possess a 247G --> T mutation, which predicts an Asp83Tyr alteration. The B genes of the other 13 cases were shown to have a G --> A mutation at the +5 nucleotide of intron 3 (intervening sequence 3 [IVS3] + 5G --> A). Reverse transcription polymerase chain reaction analysis showed that the complete exon 1-exon 7 B transcript was absent, and transcripts that skipped exon 3 were instead present in the RNA sample from the B(3) individual with the IVS3 + 5G --> A mutation. The result shows that the IVS3 + 5G --> A mutation destroys the conserved sequence of the splice donor site and leads to the skipping of exon 3 during messenger RNA processing. The B(3) transcript without exon 3 predicts a B-transferase product that lacks 19 amino acids in the N-terminal segment.

ABO Blood-Group System↗

PubMed2002

Haplotype frequencies of nine Y-chromosome STR loci in the Taiwanese Han population.

Haplotype frequencies of nine Y-chromosome STR loci (DYS19, DYS385, DYS388, DYS389I, DYS389II, DYS390, DYS391, DYS392 and DYS393) in the Taiwanese Han population were established. A total of 183 unrelated individuals produced 162 haplotypes, of which 146 were unique, 1 was found in 5 individuals, 2 were found in 3 individuals and 13 were found in 2 individuals. The haplotype diversity (99.99%) and discrimination capacity (88.5%) were calculated. A family study of 109 father/son pairs in 100 families showed 2 mutational events in the DYS389II locus and 1 in the DYS392 locus.

Adult↗

PubMed2002

Immunoglobulin allotypes among Taiwan aborigines: evidence of malarial selection could affect studies of population affinity.

The aborigines of Taiwan represent the indigenous inhabitants of the island at the time of the arrival of the Chinese from the mainland. Linguistically, the aboriginal Taiwanese are related to the Malayo-Polynesian-speaking inhabitants of Indonesia and the Philippines. Three tribes occupied lowland areas while six tribes occupied highland areas. Previous studies indicate that genetic markers associated with malaria occur in lowland populations. Though the GM haplotypes are demonstrated to be very useful in the measure of population affinities, the possibility of malarial selection on this locus could affect studies of population affinity. The present work is a case study to see whether a subdivided insular population under a possible selective load will provide divergent clustering analysis depending on the population sampled. Immunoglobulin allotype (GM and KM) profiles were generated on 230 lowland and 407 highland Taiwan Aborigines from the nine tribes. A highly significant difference in GM haplotype distribution was detected between lowland and highland populations (adjusted G = 69.408, 2 df [degrees of freedom], p < 0.00001). There were no significant differences in KM*1 frequency by altitude. The Taiwan Aboriginal GM and KM frequencies were compared to data from Indonesians, Vietnamese, Thai, Malay, Chinese from Taiwan, and Ryukyu Islanders from Okinawa using cluster analysis. The lowland populations plot among the Thai (N, NC) and Malayan Aborigines. In contrast, the highland and total Taiwan Aborigine samples plot with the Indonesian, Vietnamese, and Malayan Negrito samples. Thus, depending on the populations of Taiwan Aborigines used, different conclusions could be reached. The highland population supports the published linguistic ties; however, the lowland population does not support the linguistic relationship with Indonesian populations but is more closely related to Thai and Malays, or reflects a similar selection history.

Analysis of Variance↗