HLA—A, B, Bf Three Point Association of 1,072 Haplotypes in a German Population

Altogether 1,072 HLA-A, B, Bf haplotypes in 536 parents of 268 German families were analyzed by gene and haplotype counting in order to investigate the two and three point association of HLA-A and B antigens with Bf alleles. In agreement with previously published data (Albert et al. 1975, Bender et al. 1977) significant positive linkage disequilibria were found for HLA-A3 and BfF, B7 and BfS, B8 and BfS, Bw35 and BfF, whereas significant negative Delta values appeared to exist for HLA-A3 and BfS, B7 and BfF, B8 and BfF, B12 and BfS, as well as Bw35 and BfS. Significant positive three point Delta values were found for the following haplotypes: HLA-A11, Bw35, BfS, HLA-Aw23, Bw35, BfS, HLA-A28, B12, BfS, HLA-A2, B17, BF, HLA-A3, Bw35, BfF, HLA-Aw24, b12, BfF and HLA-A29, B12, BfF. According to the large number of comparisons performed calculating the level of significance of the three point associations, these data have to be corroborated by further investigation. The three point Delta values, obtained by calculation from the patients' phenotypes differed markedly from those results obtained by haplotype counting.     

Associations of properdin factor B with melanoma

We investigated 98 melanoma patients and 135 normal controls for differences in phenotype and genotype frequencies at the properdin factor B locus. A significant negative association with the Bf-F allele and melanoma was found, resulting in an estimated relative risk of 0.5. The estimated relative risk for developing melanoma among people with the Bf-FF genotype is 0.07. The Bf-S phenotype was significantly increased among the melanoma sample, with an estimated risk of 6.5. The data suggest association of the Bf locus with a melanoma protection and/or susceptibility gene(s).     

PROPERDIN FACTOR B POLYMORPHISM IN BLACK AMERICANS

Properdin factor B is a genetically-controlled polymorphism that can be demonstrated by agarose gel electrophoresis. The Bf gene frequencies were determined for 194 blacks from the south-eastern United States. The frequencies for Bf-F, Bf-S, Bf-F1, and Bf-Sl are 0.626, 0.327, 0.034, and 0.013, respectively. The south-eastern blacks have similar Bf frequencies to the South African blacks; however, both these groups are different from blacks from Boston. The frequency differences between south-eastern blacks and Boston blacks may be due to racial admixture differences found in the two populations.     

HLA/Bf haplotypes in a Newfoundland family

HLA/Bf haplotypes were examined in a large three-generation Newfoundland family with a high incidence of Graves' disease. In that family Graves' disease was inherited in association with the haplotype HLA Aw24, Bw39 in some instances and with HLA B8-containing haplotypes in other instances. As all seven members of the family who suffered from Graves' disease were homozygous for the Bf S allele, the study for Bf was uninformative. However, the examination of other HLA/Bf haplotypes disclosed some interesting associations. One-hundred-and-five out of 168 HLA-A, -B, -Bf haplotypes were Bf S. Although numerically deviant, no unusual HLA B/Bf associations were observed. Bf F entered the family only once. A new finding is the association between HLA B27 and Bf S1; the haplotype entered the family once and was passed on to eight family members over three generations. Bf S1 was previously reported in association with HLA B12 or W21. None of these family members had ankylosing spondylitis. The Bf allele F1 entered the family three times, always in association with HLA B18.     

HLA antigens in Bali (Indonesia) with a special reference to an isolated community

One hundred eighty-two Balinese were typed for HLA-A and -B locus antigens. From these, 103 were also typed for HLA -C, 51 for HLA-DR, 172 for Bf and 173 for GLO. These results and the significant phenotypic associations are situated with respect to other South-East Asian populations. In addition to this first study, 175 individuals from an isolated Balinese village typed for HLA-A, -B, -DR, Bf and GLO are presented, The effect of isolation on haplotype (HLA-A/-B/Bf/-DR) variability is discussed.     

HLA Antigens Associated with Properdin Factor B Allotype BfF1

Linkage disequilibrium has been described between HLA-B antigens and allotypes of properdin factor B (Bf). The association between HLA-B and DR antigens and the rare allotype BfF1 was investigated. In 27 HLA-A, B and DR typed individuals only one person was found who was DR3 negative but five who were B18 negative. Family studies showed that in nine cases B18, BfF1 and DR3 segregated as a haplotype; in another family which was B18 negative, BfF1 and DR3 segregated together. It is infered that the Bf locus is more strongly associated with HLA-DR than with HLA-B.     

ANTI-TISSUE ANTIBODIES AND IMMUNOGLOBULIN LEVELS IN RELATION TO HLA AND OTHER MARKERS IN ICELANDIC FAMILIES

Studies of 521 sera from the Icelandic cousin marriage project were made to assess the incidence of various anti-tissue antibodies and the levels of immunoglobulins, as these were considered to be useful markers of the humoral immune response. Comparisons were made between these parameters and the HLA-A and B antigens, the blood groups, the immunoglobulin allotypes (Gm, Km and Am), the properdin factor (Bf), and other markers. These investigations offered another approach to the study of the sites of action of immune response genes in man. Because the immune response may be expected to differ for each individual and depend at least in part, on the degree of exposure to different antigens, no absolute correlation was expected. There was, however, a marked association between certain IgG anti-tissue antibodies and HLA antigens. This was most marked for HLA-A10, B18 and B27, but not for HLA-A1 or B8. The comparison of immunoglobulin levels with HLA antigens, was less striking, although HLA-A2 appeared to be associated with low levels of IgE. There were also some associations between immunoglobulin levels and ABO blood groups.     

Anti-tissue antibodies and immunoglobulin levels in relation to HLA and other markers in Icelandic families.

Studies of 521 sera from the Icelandic cousin marriage project were made to assess the incidence of various anti-tissue antibodies and the levels of immunoglobulins, as these were considered to be useful markers of the humoral immune response. Comparisons were made between these parameters and the HLA-A and B antigens, the blood groups, the immunoglobulin allotypes (Gm, Km and Am), the properdin factor (Bf), and other markers. These investigations offered another approach to the study of the sites of action of immune response genes in man. Because the immune response may be expected to differ for each individual and depend at least in part, on the degree of exposure to different antigens, no absolute correlation was expected. There was, however, a marked association between certain IgG anti-tissue antibodies and HLA antigens. This was most marked for HLA-A10, B18 and b27, but not for HLA-A1 or B8. The comparison of immunoglobulin levels with HLA antigens, was less striking, although HLA-A2 appeared to be associated with low levels of IgE. There were also some associations between immunoglobulin levels and ABO blood groups.     

HLA-A,B,C and DR antigens, GLO I and Bf marker profiles in 75 Cape Coloured patients with systemic lupus erythematosus (SLE)

HLA-A,B,C and DR antigens were tested in 75 Cape Coloured systemic lupus erythematosus (SLE) patients, and the GLO I and Bf markers in 51. The patients with HLA-DR2 had a relative risk significantly greater than one (p=0.0005). Twenty-two (29%) patients had only one detectable DR antigen. Of these, 11 (50%) were found to have DR2 only. The HLA-DR7 antigen was associated with severe disease (p less than 0.02). Bf and GLO I markers were not associated with SLE.     

HLA-A, B, C, DR antigens, Bf, C4 and glyoxalase I (GLO) polymorphisms in French Basques with insulin-dependent diabetes mellitus (IDDM)

The Basques were previously shown to present a high frequency of HLA—B18 and Bf Fl. which are known to be associated with insulin dependent diabetes mellitus (IDDM). During the VIII International Histocompatibility Workshop, we studied HLA-A, B, C, DR; Bf, C4 and GLO.I polymorphisms in 51 unrelated French Basque IDDM patients and in 50 controls. Haplotypes were established by family studies in all controls and some patients. Two haplotypes were frequently found in the controls: HLA- A1, Bw57, Bf S, C4 FIS, DR7 and HLA- Aw30, Cw5, B18, Bf Fl, C4 Fs°, DR3. The first one was not found in the patients. All the components of the second haplotype had increased frequencies possibly as a consequence of linkage disequilibrium with HLA— DR3 : a highly significant association between IDDM and HLA-DR3 was observed (90.2% vs 24.0%, relative risk (RR) = 29.1. P < 10⁻¹¹). The HLA-DR4 frequency was slightly increased (37.3% vs 16.0%). and HLA—DR2 was not found. The silent allele C4 s ° was particularly associated with early diagnosed IDDM (86.7% in patients with age at onset under 20 years vs 57.1% in other patients, P < 0.02). The high relative risk for HLA-DR3/DR4 heterozygous vs that of individuals, possibly HLA-DR3 homozygous, supported the hypothesis that two HLA-DR linked genetic factors could be involved in the inheritance of IDDM susceptibility.     

HLA, A, B, C, DR, C4, Bf in insulin-dependent diabetics in the Tunisian population

There is no doubt that the autoimmune process in human disease depends on genetic factors. Varying associations were noticed between HLA DR and autoimmune disorders. The frequency of HLA-A-B and DR antigens as well as the Bf and C4 allotypes have been investigated in insulinodependant diabetes mellitus (IDDM) and compared to that of healthy controls in Tunisian population. An increase of A30, DR3, DR4, BfF1, C4AQ0 and C4BQ0 and decrease of B40, DR2, DR5 and DR6 were found in diabetes when compared to the value observation controls. The strongest association was noticed with HLA, DR3 and DR4. The prospective role of DR2 and DR5 antigens were also confirmed. Examination of HLA, Bf and C4 alleles. Two supratypes associated with IDDM have been observed among the Tunisian patients.     

A study of HLA-A, B, DR and Bf bearing haplotypes derived from 304 families resident in the north west of England

We report here haplotype frequencies for class I (HLA-A, B), class II (HLA-DR) and class III (Bf) gene products of the major histocompatibility complex (MHC) of man. As in other studies (Bertrams & Baur, 1979; Grange et al., 1981), we have chosen to document all families typed for HLA antigens and Bf phenotypes irrespective of ascertainment. We obtained 1,094 haplotypes from 304 families resident in the North West of England, of which 34.1% had been fully typed for HLA-A,B,DR and Bf polymorphisms. We have been able to find both positive and negative linkage disequilibria for two and three locus haplotypes and have listed the most commonly occurring four locus haplotypes. Our data confirms the position of the complement group between HLA-B and HLA-DR, and we have looked for evidence of segregation distortion of MHC haplotypes.     

A STUDY OF HLA-A,B, DR and Bf5 BEARING HAPLOTYPES DERIVED FROM 304 FAMILIES RESIDENT IN THE NORTH WEST OF ENGLAND

We report here haplotype frequencies for class I (HLA-A, B), class III (HLA-DR) and class III (Bf) gene products of the major histocompatibility complex (MHC) of man. As in other studies (Bertrams & Baur, 1979; Grange et al., 1981), we have chosen to document all families typed for HLA antigens and Bf phenotypes irrespective of ascertainment. We obtained 1,094 haplotypes from 304 families resident in the North West of England, of which 34·1% had been fully typed for HLA-A,B,DR and Bf polymorphisms. We have been able to find both positive and negative linkage disequilibria for two and three locus haplotypes and have listed the most commonly occuring four locus haplotypes. Our data confirms the position of the complement group between HLA-B and HLA-DR, and we have looked for evidence of segregation distortion of MHC haplotypes.     

Absence of linkage between adult polycystic kidney disease and the major histocompatibility system

Four multiplex families affected with adult polycystic kidney disease were investigated for segregation of the disease with haplotypes bearing HLA-A and B antigens and Bf allotypes. In no case did the disease travel with specific haplotypes within families showing an absence of linkage between the disease and the major histocompatability system. In addition, the disease was not associated with any HLA-A or B antigen or Bf allotype either within or among the families studied.     

HLA antigens and complotypes in insulin-dependent diabetes mellitus

One hundred and thirty-six Finnish patients with insulin-dependent (type I) diabetes mellitus were investigated for the HLA-A, B, D and DR antigens as well as the Bf and C4 allotypes. The statistically significant increase in the frequencies of HLA-A9, B8, B15, Dw3, Dw4, DR3, DR4, C4A0 and C4B3 was observed when compared with the healthy controls. About 79% of the patients had HLA-DR4, and 53% had HLA-DR3 antigens. A rare C4 allele C4B3 was found in 21% of the patients, whereas only in 2% among the controls (relative risk 16.35). The etiological fraction (EF) values indicated that HLA D/DR alleles were the best markers for IDDM, the observed EF for HLA-DR4 in diabetes was as high as 0.70. Examination of HLA, Bf and C4 phenotypes suggested that at least two supratypes "B15 BfS C4A3B3 D(R)4" and "B8 BfS C4A0B1 D(R)3" were markers for the susceptibility to type I diabetes, one third of our patients had either of these supratypes. The protective role of DR2 and Dw2 antigens was also confirmed: no HLA-Dw2 positive patients and only one with HLA-DR2 was found.     

HLA polymorphisms in Saudi Arabs

The HLA-A, -B, -C, -DR, Bf and GLO phenotypes of 109 unrelated Saudi Arab males have been determined. HLA-A and -B antigen frequencies were compared with data reported for European Caucasoids and various Arab populations. Most similarities in antigen frequencies were seen between Saudi Arab and Iraqi populations. A high frequency of Bw50 was observed in Saudi Arabs. The frequencies of HLA-DR antigens in Saudi Arabs were compared to European Caucasoids. HLA-DR7 was at high frequency in Saudi Arabs. Linkage disequilibria between alleles of HLA loci was examined. Many instances of previously reported antigen associations were seen in Saudi Arabs, together with a number of associations which have not been described elsewhere. HLA-Cw6-Bw50-DR7-BfS0.7 is suggested as being a common haplotype in Saudi Arabs.     

HLA association of idiopathic Peyronie's disease: An indication of autoimmune phenomena in etiopathogenesis?

Abstract: HLA typing for class I and class II antigens was done in 52 unrelated patients suffering from idiopathic Peyronie's disease. The controversially discussed association with the HLA-B7 cross-reacting group could not be confirmed. Marked deviations of antigen frequencies were observed for HLA-A1, B8, Cw7, DR3 and DQw2 compared to healthy local controls. After correction of p-values, Al (p_c < 0.05) and DQw2 (p_c < 0.01) remained significant. A possible association of Peyronie's disease with markers of the HLA-A1, B8, Cw7, DR3, DQw2 haplotype, as first described here, would suggest autoimmunological factors in this disorder of otherwise unknown etiopathogenesis.     

Haplotype study. Linkage between HLA-A, B, C and Bf alleles: results obtained by different statistical methods

325 HLA-A, B and Bf haplotypes obtained from family studies were investigated. In addition, 216 of these were tested for HLA-Cw2, Cw4, Cw5. Four different statistical methods were employed to study 2, 3 or 4 loci gametic associations in order to compare the results obtained by these different methods. Our results were then compared with those of other authors who employed similar methods. Piazza's method, used to identify gametic associations, was not able to show any 3 loci associations in our material. The Delta Standard Method employed in conjunction with Factorial Correspondence Analysis was found suitable for the study of chromosal prevalence in a population.     

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.     

HLA－B51与中国北方汉族中的白塞氏病相关联

对１２０例白塞氏病患者和１００名无关健康人进行了ＨＬＡ－Ａ、－Ｂ、－Ｃ、－ＤＲ和－ＤＱ抗原分型检测，并使用Ｌｙｍｐｈｏ－Ｂ－Ｋｗｉｋ分离出Ｂ－淋巴细胞进行ＨＬＡ－ＤＱ和－ＤＲ分型，用琼脂糖电泳，免疫固定等技术测定了Ｂｆ和Ｃ４同种异型。其中，５５．８３％（６７／１２０）患者中检出ＨＬＡ－Ｂ５１，而对照组仅１２％。Ｘ２和ＲＲ分别为４５．５４和９．２７（Ｐ＜０．０００５）．完全型组ＨＬＡ－Ｂ５１更为常见（６２．７９％）；除患者组的Ｃ４ＡＱ０明显高于对照组外，其它的ＨＬＡ抗原、Ｂｆ和Ｃ４同种异型无明显的组间差异。结果提示：某些内在因素，诸如免疫遗传背景（存在有与ＨＬＡ－Ｂ５１密切相关的ＢＤ易感基因）在其病因及发病机理中可能起着重要作用。