HLA associations in Italian and non-Italian Caucasoid aplastic anaemia patients

A reassessment of HLA-A and B antigen associations in patients with severe aplastic anaemia confirmed the significantly elevated frequency of HLA-A2 in Caucasoid patients reported by Albert et al. (1976). In addition, a highly significant increase in the frequency of HLA-B14 in Italian patients was observed in an initial sample of 25 patients and confirmed in a second sample of 16 patients. This latter finding was cancelled out when the Italian Caucasoid patients were pooled with the non-Italian Caucasoid patients. These results suggest that the classification of populations as "Caucasoids", without examining their ethnic origins, may introduce a serious confounding error into HLA and disease studies.     

Down subjects and Oriental population share several specific attitudes and characteristics

Down's syndrome is characterized not only by a typical "habitus", mental retardation of variable gravity and several alterations of the cardiovascular, respiratory, gastrenteric and immunitary system, but also by specific attitudes and characteristics that are in common with the Oriental population. Starting from the origin of the term mongolism, replaced with other terms such as Trisomy 21, Down's syndrome, and anomaly of Down because of the racist use made in the last century, we propose, in the light of modern knowledge about the heredity of features, a reflection on those aspects and attitudes which highlight a very particular twinning between a Down person and Asiatic peoples.     

HLA and narcolepsy in a German population

In this paper the first MHC data including HLA-A, B, C, DR, DQ and complement BF, C4A, C4B determinants in German narcoleptics are presented together with the first family studies in European Caucasoids. 57 out of 58 unrelated patients (98.3%) were positive for DR2 and DQw1, respectively. In contrast to all other reports, one patient with typical signs of narcolepsy was found to be DR2/DQw1 negative. Data showing significant increase in the frequency of B7, and normal frequencies of B35 were discordant with data from Japanese patients. Definition of the extended DR2 linked haplotypes, deduced from 6 families, revealed that 5 out of 12 were DQw1, DR2, BFS, C4B1, C4A3, B7 (Cw7), while 11/12 had DR2, DQw1, BFS, C4A3, C4B1 in common. In one multiple case family two genotypically different DR2 haplotypes were identified in affected siblings. Results from the family study were concordant with a dominant mode of inheritance with incomplete penetrance of a hypothetical disease susceptibility gene.     

HLA class I in three West African ethnic groups: genetic distances from sub-Saharan and Caucasoid populations

Fulani of Burkina Faso (West Africa) are a particularly interesting ethnic group because of their lower susceptibility to Plasmodium falciparum malaria as compared to sympatric populations, Mossi and Rimaibé. Moreover, the occurrence of a Caucasoid component in their genetic make-up has been suggested on the basis of their physical traits and cultural traditions even though this view was not supported by genetic studies. A total of 149 unrelated subjects (53 Mossi, 47 Rimaibé and 49 Fulani) have been typed for 97 HLA class I alleles with the amplification refractory mutation system/polymerase chain reaction (ARMS/PCR) technique. Mossi and Rimaibé data were pooled since none of the 42 statistically testable alleles exhibited a significant heterogeneity. These pooled gene frequencies were found to be very different from those of Fulani: a certain (P<0.001) or a likely (0.001 相似文献   

Study of HLA system in a Mataco population:

A search for antigens of the HLA system has been carried out in 53 Mataco Indians of Argentina living in a geographically isolated area in the northeast of the country. Samples were mostly collected from adults of both sexes who were not directly related.
Lymphocyte typing was performed using the microcytotoxicity technique of NIH. 118 sera specific for 15 antigens of the first HLA locus, 22 antigens of the second and 6 of the third were used.
The most frequently found alleles were HLA-A28, Aw31 and A2 for the first locus; B15 and B40 for the second; and Cw3 and Cw4 for the third.
In addition to previously published investigations on South American Indians, our typing work shows a remarkable homogeneous gene pool and a restricted range of polymorphism; therefore, a further set of haplotypes rendered us also restricted. The most frequent haplotypes that showed a significant statistical linkage desequilibrium were: A2-Cw4, A28-Bx, A2-Cw3, Aw31-Bw16, Aw24-Cw3, B15-Cw3, Bw16-Cw3 and A28-B5.
Some of these haplotypes have also been found in other indian populations.     

Killer immunoglobulin receptor gene and allele frequencies in Caucasoid, Oriental and Black populations from different continents

Parallel to the growth in interest in the past few years in the killer immunoglobulin-like receptor (KIR) genes has been the elucidation of the presence/absence of these genes and to a very limited extent, the frequency of alleles of these genes in many populations. In the present study, we have chosen seven populations to investigate the presence/absence of the KIR genes and their alleles, i.e. Cuban, Brazilian, Oman, Hong Kong Chinese, Singapore Chinese, South African Xhosa and South African San. The populations were chosen to represent different continents of the world. We show the divergence in the frequencies of these genes, and their alleles, in the different populations. Many new sequence-specific oligonucleotide probe patterns represent new alleles, each occurred in only one of the populations. The KIR gene frequencies of these seven populations were calculated and genetic distances were represented by neighbour-joining dendrograms and correspondence analyses. Also, the presence or absence of 17 KIR loci in the presently studied populations was compared with the presence or absence of the same loci in 56 worldwide populations (available on the website www.allelefrequencies.net). In total, 5134 individuals were analysed and the populations grouped, with some exceptions, according to a geographical gradient.     

Frequency of HLA-B alleles in a Caucasoid population determined by a two-stage PCR-SSOP typing strategy

High resolution PCR-SSOP typing methods for HLA-B identification have been established and applied to a Northern Ireland population, using large enough numbers to give dependable allele frequencies. The six systems, which operate independently of each other, are intended for use as secondary typing systems following HLA-B identification with a medium resolution PCR-SSOP technique.     

DPB1*7601, a novel DPB1 variant in the Caucasoid population

Abstract: A new DPB1 allele has been identified in a Caucasoid individual, DPB1*7601. The sequence of the complete second exon has been confirmed by cloning and subsequent sequencing. This allele differs by one amino acid, at codon 36, from DPB1*1401, as indicated by SBT and PCR-SSP analysis. The amino-acid motif introduced by the change is shared by DPB1*0401 and some rare alleles. It remains unclear whether the change is due to interallelic microgen conversion or a single point mutation.     

Serological identification of a non‐HLA antigen in Oriental populations

In a routine HLA antibody screening cross‐match test using the complement‐mediated lymphocytotoxicity (LCT) assay, we discovered an antibody, in a transfused Caucasian woman, recognizing an Oriental restricted antigen that does not appear to be associated with the human leukocyte antigen (HLA) system. The distribution of this ‘novel’ antigen in Oriental populations and its frequency in the Taiwanese Chinese population are reported.     

HLA polymorphisms in a Shanghai Chinese population

The frequencies of the HLA-A, B, C, D, DR and MB antigens have been determined in a homogeneous Shanghai Chinese population. Comparisons with the HLA-A and -B frequencies in other subsets of the Chinese population revealed some marked differences. No comparisons were possible for the D, DR and MB antigens since there were no previous studies of the antigens in those loci. We suggest that studies of the Chinese population should be confined to clearly defined homogeneous subsets. In this manner, the confounding effect of population heterogeneity may be avoided, and it is this heterogeneity which calls for extensive surveys of the huge Chinese population.     

Biochemical HLA typing: a population study in 112 Caucasians

In order to define frequencies and associations of biochemically defined HLA-A and -B specificities and their variants and subtypes in a Caucasian population, biochemical HLA typing was performed in a panel of 112 Austrians. Already known rare variants of HLA-A2, A3, A30, Aw33 and B39 and the more frequent subtypes of HLA-B27, B35, B44 and, in addition, a so far unknown variant of HLA-B18 were present in the panel. Family segregation analyses of the biochemically defined HLA class I variants revealed that they could be found only in certain rare haplotypes, most of them in high linkage disequilibrium. The basic variant of HLA-A30, for example, obviously occurred only in the HLA-A30, B49, Cw7 haplotype, similar to the Aw33 acidic variant, which was exclusively found in the Aw33, Bw58, Cw3 haplotype. None of the biochemical variants was found in frequent common haplotypes.     

A Comparison of HLA Data of the North American Black with African Black and North American Caucasoid Populations

For purposes of genetic comparison, the available HLA data on United States and African Black, together with United States Caucasoid populations, are summarized. Antigen frequencies and pairwise linkage disequilibria are presented for the HLA-A, -B and -C loci in Black populations typed for the 1975 Histocompatibility Testing Workshop. The Black population samples comprise 356 North American Blacks and 411 African Blacks of whom 222 were Bantu. These are compared with a sample of 503 American Caucasoids. All significant linkage disequilibria between the A and B loci found in North American Blacks were also present in the North American Caucasoids. Between the B and C loci, Bw35 and Cw4 were in strong linkage disequilibrium in all groups. Significantly stron association between the A and C loci (Aw28 with Cw3) were observed only in the African Blacks. There were unique disequilibria both in the American Caucasoids and African Blacks. Although the frequencies of many antigens in U.S. Blacks lie between those in Africans and U.S. Caucasoids, there are exceptions such as Aw33, Bw35, Cw4.     

DPB1*8601, a previously unrecognized DPB1 variant in the Caucasoid population

A new, previously unrecognized DPB1* allele, DPB1*8601, was found in a Swedish family. The new allele was carried on the common North European haplotype HLA A1-B8-DR3. Both individuals carrying the new allele were initially typed as clear DPB1*4601,*6601 but after family studies and further typing with allele-specific primers it was concluded that a new allele was present together with the common DPB1*0401. The new allele was investigated by direct sequencing of exon 2 in both forward and reverse directions employing intron primers combined with either an allele-specific sense or anti-sense biotinylated primer for bi-directional sequencing. The new allele is identical to DPB1*1701 in the five first variable regions. In the sixth region, however, DPB1*8601 carries the GGPM motif shared by several common alleles such as DPB1*0201 and 0401and 0402.     

Seronegative spondyloarthropathies and HLA antigens in a Mestizo population

HLA-A and -B antigens incidence were investigated in 100 cases of Seronegative Spondyloarthropathies and in 303 control individuals of a Venezuelan Mestizo population. Significative increased incidence of B27 was found among 69% of patients with ankylosing spondylitis and 68% with Reiter syndrome being the incidence in the control group of 2.9%. The B27 negative patients showed 40.4% positivity for Bw35, with spondylitic lesion in 12 out of 17 cases. Our results question the applicability of B27 as diagnostic criteria in the Mestizo patients bearers of a Seronegative Spondyloarthropathy and suggest the need to investigate further the role of antigens of the B locus in the pathophysiology of these clinical entities.     

HLA-linked genetic markers in Chinese and other Oriental populations

The polymorphic variants of the HLA-linked genetic markers Bf, C2, C4 and GLO—I were studied in three mongoloid populations. Analysis of linkage disequilibrium between these markers and HLA-A, B, C and DR antigens was carried out on test results from 140 unrelated Chinese individuals. The phenotypes BfS and GLO-2 were found at significantly higher frequencies than in Caucasians. BfS was associated with B12 in Japanese but not in Chinese. A single individual with the rare Bf variant SI was found. No C2 deficient individuals were observed. The C2C (common) allele occurred at a gene frequency of 0.949 and the more basic allele C2B at 0.039. The acidic variant, C2A, was observed at a frequency of 0.011 and appeared to be associated with BfF. Eighty-nine per cent of the Chinese were phenotypically C4FS. In contrast to Bf and C2, each of which is coded for by codominant alleles at a single genetic locus, C4 is coded for by two genes, C4F (Rodgers) and C4S (Chido). The C4F locus allele, C4F1 (extra fast), was strongly associated with HLA-B17, as has been found in other populations, but a new association of the C4S locus deficiency allele, C4s° (Ch-), with B17 was also observed. All HLA-B17;C4s° haplotypes were BfS positive. As has been previously found in Caucasian populations, individuals of the C4F phenotype (i.e. genotypically Fs°Fs°) were all found to be Chido negative. The frequencies of the various HLA-linked genetic markers, however, as much as the frequencies and associations of the HLA antigens themselves, distinguish these populations from other ethnic groups.     

Prognostic and predictive molecular markers in DCIS: a review

Eighteen percent of all new breast cancers detected on screening mammography are ductal carcinoma in situ (DCIS), a preinvasive lesion that is highly curable. However, some women with DCIS will develop life-threatening invasive breast cancer. Because the determinants of invasive recurrence are unknown, all women with DCIS require the same treatment (usually with surgery and radiation). Therefore, there is a need to identify biologic markers and create a profile that will provide prognostic information that is more accurate than the currently used van Nuys Index to predict invasive recurrence. In the present review, we examined the many biologic markers studied in breast cancer, describe their main biologic role and their expression in DCIS, and review the various studies regarding their ability to serve as prognostic factors in breast cancer with an emphasis on predicting invasive recurrence in patients with DCIS. This review covers established markers, namely, ER, PR and HER2/neu, that are used routinely to make treatment decisions as well as investigative biologic factors involved in cell proliferation, cell cycle regulation, extracellular molecules, factors involved in extracellular matrix degradation, and angiogenesis. However, controversies exist regarding the value of these prognostic factors, their interrelationship, and their advantages over morphologic evaluation.     

Target molecular treatment markers in Intrahepatic Cholangiocarcinoma based on Chinese population

BackgroundAs more and more molecular markers have been identified in Intrahepatic Cholangiocarcinoma (ICC), target treatments are promising all around the world. However, geographical and ethnic variations in the ICC epidemiology suggest different genetic variance prevalence in western and eastern countries.MethodsSix genetic variations in Chinese ICC populations were analyzed by fluorescent in situ hybridization (FISH) or Sanger sequencing, listed as IDH1/2 mutation, FGFR2 translocation, NTRK1 amplification, MDM2 amplification, HER2 amplification and MET amplification, all of which have corresponding target drugs; meanwhile, they were compared with these gene prevalence in Spanish population based on the cBioPortal database.ResultsThe incidences of IDH1/2 mutation, FGFR2 translocation, NTRK1 amplification, MDM2 amplification, HER2 amplification and MET amplification were 29.5 %, 12.9 %, 1.51 %, 2.27 %, 3.03 % and 0.75 %, respectively, in the Spanish population and 7.14 %, 5.71 %, 7.86 %, 5.71 %,4.29 % and 2.14 %, respectively, in the Chinese population. For the gene NTRK1, 11 samples showed signal apart companied amplified using FISH break-apart probes but none of them demonstrated genetic fusion by next-generation sequencing. As to clinicopathological characteristics, patients carrying IDH1/2 mutation showed longer overall survival in the Chinese population, while those carrying FGFR2 translocation tended to be younger in the Spanish population. For HER2, MDM2 and MET, gene amplification predicted protein high-expression, whereas FGFR2 translocation and NTRK1 amplification did not predict protein high-expression.ConclusionsAlthough many target drugs have been speeded up for approval such as BGJ398 for FGFR2 fusion positive ICC patients in western countries, the beneficiary populations are very small in China. The regular target drug such as trastuzumab for HER2 amplification and Crizotinib for MET amplification may be potential candidates in target treatment based on the Chinese population.