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Biomedical subjects

B R Hawkins

Publications and source records attributed to B R Hawkins.

At least 37 records · Page 2Linked to original sources

Highly successful long-term outcome of kidney transplantation in Chinese recipients: an enhancing race effect?

We report on 352 cadaveric kidney transplants and 294 living related transplants performed over a 25-yr period among the Chinese population of Hong Kong. There is a marked preference for transplanting male patients, especially from living donors, and we argue that this represents a cultural phenomenon within the Chinese population. The 10-yr graft survivals for related and cadaveric transplants are 86.2% and 67.4%, respectively. These figures are appreciably higher than corresponding figures in Caucasian populations. We show beneficial effects of using cyclosporin A, minimizing the cold ischemia time and avoiding very young and very old donors. There is a clear benefit of transplanting kidneys with zero or one mismatched HLA antigen against the recipient but no stepwise decrease in outcome as the number of mismatched antigens increases. There is close concordance between the outcome of living related grafts with zero, one, and two mismatched haplotypes against the recipient and no observable benefit of haplotype matching. We show that Chinese renal transplant recipients in other centers also have better long-term graft outcome than Caucasians, both for cadaveric and living related transplants. We draw attention to the existence of a detrimental "race effect" in other studies when Black recipients are compared with Caucasians and consider whether an enhancing race effect exists for Chinese or whether the better outcome reflects different underlying diseases in Chinese.

Actuarial Analysis↗

Incidence of graft-versus-host disease in Hong Kong Chinese and its influence on survival after bone marrow transplantation from HLA-identical siblings.

Graft-versus-host disease (GVHD) is an important complication of allogeneic bone marrow transplantation (BMT). To assess its influence on transplant outcome, we studied 90 Chinese patients with hematologic disorders with BMT from HLA-identical siblings. GVHD prophylaxis consisted of a combination of methotrexate (MTX) and cyclosporine A (CsA). The incidence of grade II-IV acute GVHD was 29% (95% CI 19-38%). The incidence of limited and extensive chronic GVHD was 30% (95% CI 20-40%). For patients transplanted for early hematologic malignancy (n = 40), those with GVHD (acute and/or chronic) had lower relapse rate (17% (95% CI 0-36%) vs. 54% (95% CI 26-82%), P = 0.043). They had higher transplant-related mortality (12% (95% CI 0-28%) vs. 6% (95% CI 0-18%), P = 0.715) and event-free survival (EFS) (73% (95% CI 53-93%) vs. 43% (95% CI 17-69%), P = 0.104) that had not reached statistical significance. For patients transplanted for advanced hematologic malignancy (n = 37), those with GVHD also had lower relapse rate (5% (95% CI 0-15%) vs. 72% (95% CI 50-94%), P = 0.002) and higher transplant-related mortality (50% (95% CI 27-73%) vs. 8% (95% CI 0-24%), P = 0.006) than those without any GVHD. They had higher EFS (47% (95% CI 24-70%) vs. 26% (95% CI 5-47%), P = 0.609) that had not reached statistical significance. Therefore, the incidence of acute and chronic GVHD in Chinese was similar to that of their Caucasian counterparts using MTX and CsA for GVHD prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Analysis of a Chinese population suggests that the TNFB gene is not a susceptibility gene for Graves' disease.

Graves' disease is associated with different HLA genes in different races. The TNFB gene lies between the class I and class II HLA genes and has two alleles, TNFB*1 and TNFB*2. Studies in Caucasians have suggested that the TNFB gene might be a susceptibility gene for Graves' disease. To investigate further the role of TNFB in predisposition to Graves' disease, we determined whether the TNFB disease associations in the Chinese were similar to those in Caucasians. A total of 57 patients with Graves' disease (32 male) were studied. A TNFB gene fragment was amplified from genomic DNA by using the polymerase chain reaction and digested with Nco I to distinguish the TNFB alleles (TNFB*1 and TNFB*2). Genotype frequencies were compared with those in a racially matched group of 92 controls. TNFB*1 homozygosity occurred in 15 (26%) Graves' and 22 (24%) control subjects. TNFB*1/TNFB*2 heterozygosity occurred in 29 (51%) and 48 (52%) and TNFB*2 homozygosity in 13 (23%) and 22 (24%), respectively (NS). There were gender differences in the frequencies of TNFB*1 homozygosity (13 male [41%], 2 female [8%]). TNFB*1/TNFB*2 heterozygosity (13 male [41%], 16 female [64%]) (chi 2 = 7.3, p = 0.02), and TNFB*2 frequency (19 male [59%], 23 female [92%]; pc = 0.04) in Graves' patients. We conclude that the TNFB associations with Graves' disease in the Hong Kong Chinese differ between the genders and from those described in Caucasians. The TNFB gene is not a susceptibility gene for Graves' disease.

Asian People↗

The HLA association with Graves' disease is sex-specific in Hong Kong Chinese subjects.

OBJECTIVE: Graves' disease is associated with different HLA genes in Caucasians and the Chinese, in whom the HLA associations may be stronger in males than females. Common HLA-associated susceptibility in both races may occur at the HLA-DQ loci. The aims of this study were to examine the HLA-A, B, DR and DQ associations with Graves' disease in a Hong Kong Chinese population and to determine whether the HLA associations differ between the sexes and between subjects with and without thyrotoxic periodic paralysis. DESIGN: HLA-A, B and DR types were determined by serological typing and DQA1 and DQB1 alleles by oligonucleotide probing of the respective enzymatically amplified gene. PATIENTS: Ninety-seven Chinese patients with Graves' disease (31 males with, 35 males without and 31 females without thyrotoxic periodic paralysis) and 105 racially matched healthy controls. MEASUREMENTS: Frequencies of HLA types/alleles at each locus were compared between patients and controls and between the Graves' subgroups using the chi 2-test. RESULTS: HLA-B46, DR9 and DQB1*0303 were associated with Graves' disease in males only; these associations were weaker in males with thyrotoxic periodic paralysis. DR12, DQA1*0401 and DQB1*0301 were protective, regardless of sex or the presence of thyrotoxic periodic paralysis. The positive HLA associations in the Hong Kong Chinese were distinct from those in Caucasians whereas the protective haplotype was similar to that described in Caucasians. CONCLUSIONS: These findings call in question the role of HLA genes in disease susceptibility but suggest a role for HLA in protection from Graves' disease.

Adult↗

HLA-DPB1 alleles correlate with risk for multiple sclerosis in Caucasoid and Cantonese patients lacking the high-risk DQB1*0602 allele.

Multiple sclerosis (MS) is a demyelinating disease associated with the HLA-DR2-related haplotype DRB1*1501, DQB1*0602 in Caucasoids and with DQB1*0602 in DR2-positive Cantonese. However, many MS patients do not have the high-risk HLA-D determinants and alternative genes may contribute to the pathogenesis of MS. One candidate gene is HLA-DPB1. Our reanalysis of five earlier reports of HLA-DPB1 antigen distributions in Caucasoid MS patients shows a consistent and highly significant increase (p = 1.5 x 10(-5)) in frequency of HLA-DPw3 in the combined data set. This study tests whether HLA-DPw3 (DPB1*0301) is also increased in frequency in Australian and Cantonese MS patients and whether any distortion in DPB1 allelic distributions can be attributed to linkage disequilibrium with DQB1*0602. PCR-RFLPs were used to determine distributions of 20 HLA-DPB1 alleles in 41 Australian MS patients and 67 controls of known DQB1*0602 status and in 11 Cantonese MS patients and 33 controls positive for HLA-DR2. HLA-DP distributions in Australian MS patients and controls positive for DQB1*0602 did not differ, but in those MS patients lacking DQB1*0602, the DPB1*0301 antigen (phenotype) frequency was significantly (p = 0.006) increased (50.0%) when compared with DQB1*0602-negative controls (9.1%). DPB1*0301 was associated (p = 0.003) with DQB1*0402 (DR8) in Caucasoid MS patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗

Restriction fragment length polymorphism of HLA-DQ and -DR allogenotypes in normal southern Chinese.

We have examined the Taq I restriction fragment length polymorphism (RFLP) of the MHC class II regions of 96 normal Southern Chinese with respect to the HLA-DRB, -DQA, and -DQB genes. The data were compared with the DR and DQ serotyping. RFLP correlates well with the serological typing of the DR types of Chinese. Variants are seen in DR2 and DR12. The variant in DR12 with a 10 kb at the upper band (DR12b) is not found in Caucasoids and is more frequent in Chinese (19.4% of the alleles). With the help of DQA and DQB RFLP the assignment of genotyping of DRB types is facilitated. Some of the linkage disequilibrium patterns among DRB, DQA and DQB are different from Caucasoids. This is particularly obvious in the DR2 and DR5 haplotypes. In the 96 Southern Chinese, the 3 commonest haplotype frequencies are: DR12b, DQ alpha 1b, DQ beta 3b (18.3%); DR9, DQ alpha 3, DQ beta 3a (15.7%); DR4, DQ alpha 3, DQ beta 3a (14.2%). The various DR beta, DQ alpha. DQ beta genes can be accurately defined in Chinese by RFLP. Polymerase chain reactions using sequence-specific primers were performed to confirm the various HLA-DRB and -DQB alleles. The use of RFLP is important in the study of HLA matching and HLA-disease association in Southern Chinese.

Asian People↗

Myasthenia gravis in Hong Kong Chinese. 1. Epidemiology and adult disease.

A territory-wide study of myasthenia gravis (MG) was conducted in Hong Kong. Two hundred and sixty-two Chinese patients (159 adult and 103 paediatric onset) were identified, corresponding to a point prevalence and period prevalence of 53.5 and 62.2 per million respectively, and an average annual incidence of 4.0 per million population. Nine patients died, 7 from MG, giving a case fatality rate of 0.027. Female predominance was present in the whole group of patients (female to male ratio 1.6:1) and in those with adult disease (ratio 2.1:1), but not in those with onset in childhood (ration 1.1:1). Onset of disease was most common in the first 3 decades of life, and became less common in subsequent decades. Juvenile onset MG occurred in 39.3% of patients and restricted ocular MG in 47.9%. Familial occurrence was found in 5 patients. In the 159 adult onset patients, ocular disease was most common (32.7%), followed by mild generalised (29.6%), moderately severe generalised (24.5%), fulminating (11.9%) and late severe disease (1.3%). The mean age of onset of symptoms was 36.7 years. The symptomatology was similar to that of Caucasoid populations. Autoimmune thyroid disease was the commonest associated disease, and the incidence of thymoma among thymic abnormalities was high at 38%.

Adolescent↗

Myasthenia gravis in Hong Kong Chinese. 2. Paediatric disease.

In a study covering 85% of the population of Hong Kong, 39% of all myasthenia gravis (MG) patients, i.e. 103 individuals (54 girls and 49 boys) were found to have had MG with onset before puberty. Two patients had transient neonatal MG, 20 had early onset juvenile MG and 81 had late onset juvenile MG. Restricted ocular MG occurred in 71% of patients and the remainder had generalised MG. The median age at onset was 4 years. Complete remission occurred in 34 patients (34%), a good response in 14 (14%), and fair response in 32 (32%). The clinical course remained static in 16 patients (16%) and 3 patients deteriorated. Two patients died, 1 with myasthenic crisis and the other with cholinergic crisis. All patients, except 2 with neonatal MG, were initially treated with anticholinesterase, but 24% also required steroid therapy. Thymectomy was performed for 12 patients, of whom 5 (42%) showed marked improvement. Thymic histology was normal in 3, showed hyperplasia in 6, non-invasive thymoma in 1 and involution in 2. The most commonly associated disease was Graves' disease which occurred in 7 patients (7%).

Adolescent↗

Susceptibility to IDDM in a Chinese population. Role of HLA class II alleles.

MHC associations with IDDM in a Chinese population were studied to investigate genetic susceptibility to the disorder. The frequency of HLA-DR3 was significantly higher in the diabetic patients (19/49 [38.7%] vs. control subjects, 11/105 [10.5%], Pc less than 1.3 x 10(-3), RR = 5.3 [CI 2.3-12.1]), whereas DR4 was not (11/49 [22.4%] vs. 28/105 [26.7%], NS). The frequency of DR3/4 heterozygosity was higher in the diabetic patients (6/49 [12.2%] vs. control subjects, 0/105 [0%], P = 1.7 x 10(-3), RR = 31.5 [CI 3.8-263.6]). The frequency of DR3/9 heterozygosity also was higher in the diabetic patients (6/49 [12.2%] vs. control subjects, 2/105 [1.9%], P = 0.03, RR = 6.2 [CI 3.0-12.7]). No significant associations were noted between DQB1 alleles and IDDM. Among DR4-positive subjects, the frequency of DQB1 allele DQB1*0302 was higher in the diabetic patients (10/11 [90.0%] vs. control subjects, 12/24 [50%], Pc less than 0.05, RR = 7.0 [CI 1.3-38.0]), and the frequency of DQB1*0401 was significantly lower in the diabetic patients (2/11 [18.2%] vs. control subjects, 16/24 [66.7%], Pc = 0.04, RR = 0.1 [CI 0.02-0.46]). No DR4 subtype was associated significantly with IDDM. The frequency of DQA1*0501, a DQA1 allele, was higher in diabetic patients (22/41 [53.7%] vs. control subjects, 20/95 [21.1%], Pc less than 3 x 10(-3), RR = 4.3 [CI 2.0-9.3]). The frequency of DQA1*0301, which has been associated consistently with IDDM in other ethnic groups, was not significantly higher in the diabetic patients in this study (27/41 [65.9%] vs. control subjects, 53/95 [55.8%], NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗

The new HLA.

The application of molecular genetics and biochemical techniques to the study of the HLA system over the past few years has resulted in tremendous advances in our knowledge of this area of the human genome. In this article, we describe the "new HLA" that has been pieced together recently through the combined efforts of molecular geneticists, biochemists, and HLA serologists, as well as developments in attempts to elucidate the associations of HLA antigens and disease.

Biochemical Phenomena↗

Immunogenetics in Chinese patients with SLE.

100 consecutive Chinese patients with SLE were recruited for study of HLA-A, B and DR antigen. Clinical and serological parameters were analysed with respect to the HLA antigens. B5 was associated with presence of other autoimmune diseases (thyrotoxicosis, myasthenia gravis, diabetes mellitus, corrected p less than 0.025); absence of malar rash (corrected p less than 0.025); B35, with male sex (corrected p less than 0.025); DR2 with anti-Ro (anti-SSA) antibody (p less than 0.05). Previous study of association with B13, B17 was not present in our cohort. Except for malar rash, subclassification of disease status with respect to HLA antigen did not reveal significant association.

Adult↗

Multiple sclerosis amongst Chinese in Hong Kong.

A territory-wide investigation of southern Chinese patients with multiple sclerosis (MS) was conducted in Hong Kong. There were 47 patients, 35 of whom were clinically definite (CDMS), 6 laboratory-supported definite (LSDMS) and 6 clinically probable (CPMS). The prevalence rate was 0.88 per 10(5) population, which is of the same order as in other Oriental populations but much lower than in Caucasoid populations. Comparisons with major Oriental and Caucasian series showed essentially the same clinical picture with only minor variations. In one autopsy case, the lesions were found mainly in the optic nerves and spinal cord, with marked softening in addition to the classical demyelination features. In contrast to findings in Caucasians, the detection rate of oligoclonal bands in the cerebrospinal fluid was low (33% in CDMS patients) and there was no association with human leucocyte antigens. The possible implications of these findings on the pathogenesis of MS are discussed.

Adult↗