Role of HLA-B and C alleles in development of psoriasis in patients from North India

Abstract: The association of HLA antigens with susceptibility for development of psoriasis vulgaris has been studied mostly using serologic methods. A number of different HLA class I antigens have been reported to be associated with predisposition to develop this disease. While Cw6 is the allele most commonly thought to confer risk for psoriasis, a number of HLA-B locus alleles have also been thought to be involved and, recently, in at least three studies, a specific amino acid in the HLA-C heavy chain has been implicated. With the recent development of molecular methods for typing for HLA class I alleles, it has become possible to re-examine this association by performing high resolution typing. In the present study we have investigated 38 psoriasis patients and 84 ethnically and geographically matched controls from North India. They were typed for HLA-B and HLA-C. The results showed the Cw*0602 was the main allele that was increased in this group of patients. The previously reported association with alanine-73 was not found to be significant. Cw*0602 was found in 71% of the patients. B*5701 and B*3701 were also increased but appeared to be secondary to linkage disequilibrium with Cw*0602.     

The MICA-A4 triplet repeats polymorphism in the transmembrane region confers additional risk for development of psoriatic arthritis in the Croatian population.

The aim of this study was to investigate possible differences in the frequencies of alleles at the HLA loci and at microsatellite loci within the HLA region among patients suffering from psoriatic arthritis (PsA) and healthy controls. Fifty-eight Croatian PsA patients (28 male and 30 female) and 157 healthy unrelated controls were typed for HLA alleles (A, B, Cw and DRB1) by the polymerase chain reaction-sequence-specific primers (PCR-SSP) method, while microsatellite alleles (D6S265, D6S273, MHC class I chain-related gene (MICA) and MIB) were analysed by electrophoresis in an ALFexpress sequencer (Pharmacia Biotech, Uppsala, Sweden). The findings from this study were: (1) the frequencies of B*39 and B*57 were significantly increased in PsA patients; (2) differences in the frequencies of B*13 and B*27 were not statistically significant after correction; (3) the B*0702, B*18, and B*38 alleles were decreased in patients only before correction; (4) none of the alleles at other HLA loci tested were associated with PsA in Croatia; (5) polymorphism at D6S265, D6S273, and MIB microsatellites in patients did not show any statistically significant differences when compared to controls; (6) the increase in the MICA-A4 allele frequency in PsA patients was independent of the B*39 and B*57 alleles.     

The MICA‐A4 triplet repeats polymorphism in the transmembrane region confers additional risk for development of psoriatic arthritis in the Croatian population

The aim of this study was to investigate possible differences in the frequencies of alleles at the HLA loci and at microsatellite loci within the HLA region among patients suffering from psoriatic arthritis (PsA) and healthy controls. Fifty‐eight Croatian PsA patients (28 male and 30 female) and 157 healthy unrelated controls were typed for HLA alleles (A, B, Cw and DRB1) by the polymerase chain reaction–sequence‐specific primers (PCR‐SSP) method, while microsatellite alleles (D6S265, D6S273, MHC class I chain‐related gene (MICA) and MIB) were analysed by electrophoresis in an ALFexpress sequencer (Pharmacia Biotech, Uppsala, Sweden). The findings from this study were: (1) the frequencies of B*39 and B*57 were significantly increased in PsA patients; (2) differences in the frequencies of B*13 and B*27 were not statistically significant after correction; (3) the B*0702, B*18, and B*38 alleles were decreased in patients only before correction; (4) none of the alleles at other HLA loci tested were associated with PsA in Croatia; (5) polymorphism at D6S265, D6S273, and MIB microsatellites in patients did not show any statistically significant differences when compared to controls; (6) the increase in the MICA‐A4 allele frequency in PsA patients was independent of the B*39 and B*57 alleles.     

Polymorphism in MICA rather than HLA-B/C genes is associated with psoriatic arthritis in the Jewish population

The aim of this study was to examine whether the association of psoriatic arthritis (PsA) with human leukocyte antigen (HLA) class I genes is secondary to linkage disequilibrium with a nearby gene. We examined a sample of the Jewish population to investigate whether HLA-B/C and DR polymorphism is associated with susceptibility, or whether other closely related class I loci, such as the major histocompatibility complex class I chain-related gene A (MICA) and tumor necrosis factor (TNF), might play a role in disease development. Comparisons of different populations with different HLA profiles would be of value in identifying the candidate genes involved in PSA. Fifty-two patients with PsA and 73 random matched controls from a Jewish population were selected and DNA typed by polymerase chain reaction-single-strand oligonucleotide probe (PCR-SSOP) (HLA-C), PCR sequence-specific primers (PCR-SSP) (HLA-B, -DR), radioactive PCR (MICA-TM polymorphism in the transmembrane region), and PCR-RFLP (TNF). Some findings can be concluded from the study: (1) the frequency of HLA-B*5701, B*3801, B*39, B*27, Cw*0602, Cw*07, DRB1*0402, and DRB1*0701 were not found to be significantly increased in PsA; (2) no significant differences of TNFalpha promoter alleles at positions -308 and -238 were found between PsA and healthy controls; (3) the trinucleotide repeat polymorphism MICA-A9 was present at a higher frequency in PsA patients, (p(c) < 0.009, RR = 3.34, EF = 0.39); and (4) MICA-A9 polymorphism was found in linkage disequilibrium with HLA-B alleles (B*5701, B*3801) described to be associated with PsA in Caucasians. These results suggest that the MICA gene or other nearby gene(s) may be involved in the development of PsA, and it would thus appear that psoriasis vulgaris (PsV) and PsA are associated with different MHC susceptibility genes.     

Association of an extended haplotype of HLA class I alleles and their flanking microsatellites with spondyloarthropathies in South Indian patients

Spondyloarthropathy (SpA) is a complex autoimmune disease known to have an association with the HLA system. The aims of the present study were to compare the suballelic association of HLA-B27 and other HLA class I genes with microsatellite markers spanning the HLA class I region in the South Indian population of Kerala. The five microsatellites were C1_2_A (D6S2793), C1_2_5 (D6S2811), C1_4_1 (D6S2927), MIB (D6S2810), and STR-MICA. HLA typing was performed in 67 SpA patients and 77 ethnically matched healthy controls by polymerase chain reaction using sequence-specific primers, whereas fluorescence-labeled microsatellites were analyzed using GeneScan analysis. There was a significant association of HLA-B27 and Cw*02 with SpA, whereas B*44 had a negative association with the disease. Only two HLA-B27 subtypes, B*2704 and B*2705, were observed in the South Indian population. We were able to successfully predict the major B27 subtype B*2705 based on the C1_2_5 microsatellite. A significant association of different alleles of all the microsatellite markers with SpA was observed. An extended six-locus haplotype, B*2705-Cw*02-STR-MICA(A4)-C1_4_1 (213 bp)-C1_2_5 (178 bp)-MIB (340 bp), was significantly associated with SpA.     

HLA-A*9, a probable secondary susceptibility marker to ankylosing spondylitis in Basque patients

HLA-B27 is strongly associated to ankylosing spondylitis (AS). The objective of our study was to analyze HLA-B27 association, B27 subtype distribution and frequency of other HLA class I and DR antigens in a group of Basque AS patients. HLA class I antigens were typed serologically and HLA-B27 and A9 subtypes were determined by DNA typing in samples from 46 patients with AS, 54 B27-positive spondyloarthropathies, 82 healthy subjects and 20 B27-positive controls. A class I HLA 9.2 kb PvuII restriction fragment length polymorphism (RFLP), previously associated with AS, was analyzed in a representative group of patients and controls. We found that HLA-B*2705 conferred a relative risk of 126 for AS in this group. HLA-A9 (A*2402) allele was significantly increased in AS patients compared with healthy controls and B27-positive control group (Pcorr<0.0001) and also increased in patients affected with peripheral arthritis. No association between class I HLA 9.2 Kb RFLP and AS was found. These results suggest that HLA-A*9 allele itself or another linked gene could act as a secondary and independent susceptibility allele to AS.     

Characteristics of HLA class I and class II polymorphisms in Rwandan women

OBJECTIVE: To define HLA class I and class II polymorphisms in Rwandans. METHODS: PCR-based HLA genotyping techniques were used to resolve variants of HLA-A, B, and C to their 2- or 4-digit allelic specificities, and those of DRB1 and DQB1 to their 4- or 5-digit alleles. RESULTS: Frequencies of 14 A, 8 C, and 14 B specificities and of 13 DRB1 and 8 DQB1 alleles were >/=0.02 in a group of 280 Rwandan women. These major HLA factors produced 6 haplotypes extending across the class I and class II regions: A*01-Cw*04-B* 4501-DRB1*1503-DQB1*0602 (A1-Cw4-B12- DR15 - DQ6), A * 01 - Cw * 04 - B * 4901 -DRB1 * 1302-DQB1*0604 (A1-Cw4-B21-DR13-DQ6), A*30 - Cw*04 - B*15 - DRB1*1101 - DQB1*0301 (A19-Cw4-B15-DR11-DQ7), A*68-Cw*07-B* 4901-DRB1*1302-DQB1*0604(A28-Cw7-B21- DR13 - DQ6), A*30 - Cw*07 - B*5703 - DRB1* 1303-DQB1*0301(A19 - Cw7 - B17 - DR13 - DQ7), and A*74-Cw*07-B*4901-DRB1*1302-DQB1* 0604 (A19-Cw7-B21-DR13-DQ6), respectively. Collectively, these extended haplotypes accounted for about 19% of the total. Other apparent class I-class II haplotypes (e.g., Cw*17-B*42-DRB1*0302-DQB1*0402, Cw*06- B*58-DRB1*1102-DQB1*0301, and Cw*03- B*15-DRB1*03011-DQB1*0201) did not extend to the telomeric HLA-A locus, and other 3-locus class I haplotypes (e.g., A*68-Cw*04-B*15, A*74-Cw*04-B*15, and A*23-Cw*07-B*4901) completely or partially failed to link with any specific class II alleles. DISCUSSION: Frequent recombinations appeared to occur between the three evolutionarily conserved HLA blocks carrying the class I and class II loci. The HLA class I profile seen in Rwandans was not directly comparable with those known in the literature, although the class II profile appeared to resemble those in several African populations. These data provide additional evidence for the extensive genetic diversity in Africans.     

Characterization of the HLA class I genotypes of a Venezuelan Amerindian group by molecular methods

Abstract: We have characterized the HLA class I genotypes of the Yucpa, a tribe of Venezuelan Amerindians, using molecular methods. The study was carried out on DNA extracted from unrelated individuals using low resolution ARMS-SSP typing with sequence-specific primers, high resolution typing using reference strand conformation analysis (RSCA), and for some samples sequence-based typing (SBT). The following class I alleles were found to be present in this tribe: for the HLA-A locus A*0204, A*0212, A*0213, A *2402, A*3101 and A*6801; for the B locus B *1522, B *3512, B*3905, B *3909, B*4004 and B*52012, and for C locus Cw *0102, Cw*0302/4, Cw*0401, Cw*0702 and Cw*1503. This is the first rime these alleles have been described in this group, although all of them have previously been reported as being present in other Amerindian tribes. The study confirmed the high frequency of HLA-B39 which was previously observed in serologi-cal analysis of this tribe, and indicated that two different B*39 alleles were present in this population. The identification of the class I alleles by molecular methods for this ethnic group confirms the restricted polymorphism of the MHC molecules previously obtained by serology and has allowed a more accurate definition of the different alleles present in this population.     

Paroxysmal nocturnal hemoglobinuria: significant association with specific HLA-A, -B, -C, and -DR alleles in an Italian population

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by the expansion of a PIG-A mutated hematopoietic stem cell. An immune-mediated origin has been suggested for this disease. Because HLA genes represent a susceptibility factor for autoimmunity, we investigated HLA genotype in 42 Italian PNH patients compared with 301 control subjects of the same ethnic origin. A significantly increased frequency of the HLA class I alleles A*0201 (p < 0.05), B*1402 (p < 0.001), and Cw*0802 (p < 0.005), and of the HLA class II DRB1*1501 (p < 0.01) with the linked DQB1*0602 (p ≤ 0.05) and DRB1*01 (p ≤ 0.05) with the linked DQB1*0501 (p ≤ 0.01) alleles, has been observed. Notably, a fourfold increase of the haplotype B*1402, Cw*0802 (p < 0.0005) and a 15-fold increase of the Mediterranean haplotype A*33, B*1402, Cw*0802, DRB1*0102, DQB1*0501 (p < 0.005) was also revealed. This association may provide new insights into the autoimmune pathogenesis of PNH.     

The influence of human leukocyte antigen class I alleles and their population frequencies on human immunodeficiency virus type 1 control among African Americans

Populations of African ancestry continue to account for a disproportionate burden of the human immunodeficiency virus type 1 (HIV-1) epidemic in the United States. We investigated the effects of human leukocyte antigen (HLA) class I markers in association with virologic and immunologic control of HIV-1 infection among 338 HIV-1 subtype B-infected African Americans in 2 cohorts: Reaching for Excellence in Adolescent Care and Health (REACH) and HIV Epidemiology Research Study (HERS). One-year treatment-free interval measurements of HIV-1 RNA viral loads and CD4(+) T cells were examined both separately and combined to represent 3 categories of HIV-1 disease control (76 controllers, 169 intermediates, and 93 noncontrollers). Certain previously or newly implicated HLA class I alleles (A*32, A*36, A*74, B*14, B*1510, B*3501, B*45, B*53, B*57, Cw*04, Cw*08, Cw*12, and Cw*18) were associated with 1 or more of the endpoints in univariate analyses. After multivariable adjustments for other genetic and nongenetic risk factors of HIV-1 progression, the subset of alleles more strongly or consistently associated with HIV-1 disease control included A*32, A*74, B*14, B*45, B*53, B*57, and Cw*08. Carriage of infrequent HLA-B but not HLA-A alleles was associated with more favorable disease outcomes. Certain HLA class I associations with control of HIV-1 infection cross the boundaries of race and viral subtype, whereas others appear confined within one or the other of those boundaries.     

Polymorphism of HLA class I genes in Meizhou Han population of Guangdong, China

Human leukocyte antigen (HLA) is an invaluable marker for anthropological studies because of its extreme polymorphism. Most of the studies carried out in Chinese populations are about HLA class II genes, but few about class I genes. In the present study, we investigated HLA class I polymorphism using polymerase chain reaction-sequencing-based typing (PCR-SBT) method in 104 unrelated Han individuals in Meizhou of Guangdong, southern China. Twenty-three HLA-A, 43 HLA-B and 27 HLA-C alleles were identified and allele frequencies and two-locus (C/B) and three-locus (A/C/B) haplotypes were statistically analysed. The most frequent HLA-A allele is A*110101 with a frequency of 30.3%, followed by A*24020101 (22.2%) and A*2420 (11.6%). Among the 43 detected HLA-B alleles, B*5801 (17.0%), B*400101 (15.5%) and B*4601 (10.0%) were frequently observed. Among the 27 detected C alleles, the most predominant one is Cw*07020101 (25.8%), followed by Cw*0717 (14.7%). The most frequent HLA-C/B two-locus haplotype is Cw*07020101/B*400101 (10.1%). The most common HLA-A/C/B three-locus haplotype in Meizhou Han is A*110101/Cw*07020101/B*400101 (3.4%). Phylogenetic tree based on HLA class I allele frequencies genetically suggested that Meizhou Han has an affinity to southern Asian populations. The result may also reflect an admixture of Han and ethnic minorities of southern China.     

Sequence-based typing of HLA class I alleles in Alaskan Yupik Eskimo

In comparison to South America, native North Americans tend to be less diverse in their repertoire of HLA class I alleles. Based upon this observation, we hypothesized that the Yupik Eskimo would exhibit a limited number of previously identified class I HLA alleles. To test this hypothesis, sequence-based typing was performed at the HLA-A, -B and -C loci for 99 Central Yupik individuals from southwestern Alaska. Two new class I alleles, A*2423 and Cw*0806, were identified. While A*2423 was observed in only one sample, Cw*0806 was present in 26 of the 99 individuals and all of the Cw*0806 samples contained B*4801. Allele Cw*0806 differs from Cw*0803 by a single nucleotide substitution such that Cw*0803 may be the progenitor of Cw*0806. Allele Cw*0803 was originally characterized as unique to South America, but detection of Cw*0803 in the Yupik indicates that Cw*0803 was a founding allele of the Americas. The presence of new alleles and previously unrecognized founding alleles in the Yupik population show that natives of North America are more diverse than previously envisioned.     

Polymorphism of HLA class I genes in the Brazilian population from the Northeastern State of Pernambuco corroborates anthropological evidence of its origin

The allelic distribution of human leukocyte antigen (HLA) class I genes (HLA-A, HLA-B, and HLA-Cw) of the population from the State of Pernambuco in Northeastern Brazil was studied in a sample of 101 healthy unrelated individuals. Low to medium resolution HLA class I typing was performed using polymerase chain reaction-amplified DNA hybridized to sequence specific primers (PCR-SSPs). Twenty allele groups were detected for HLA-A, 28 for HLA-B, and 14 for HLA-Cw. The most frequent alleles were HLA-A*02(0.2871), HLA-B*15(0.1238), and HLA-Cw*04(0.2277), and the most frequent genotypes were A*02/A*02(0.0990), B*15/B*15(0.0594), and Cw*04/Cw*04 and Cw*07/Cw*07, both with a frequency of 0.0792. The observed heterozygosity for the studied loci was 79.21% for HLA-A, 87.13% for HLA-B, and 77.23% for HLA-Cw. The most frequent haplotype was A*02-Cw*04-B*35(0.0485), which is also present in Western European, Amerindian, and Brazilian Mulatto populations, but absent in African populations. Taken together, these data corroborate the historic anthropological evidences of the origin of the Northeastern Brazilian population from Pernambuco.     

Association of HLA DQ B1<Superscript>*</Superscript> and HLA DR B1<Superscript>*</Superscript> Alleles with Goitrous Juvenile Autoimmune Hypothyroidism—A Case Control Study

The present study was designed to analyze the distribution of HLA DQ B1* and DR B1* in patients with goitrous juvenile autoimmune hypothyroidism from Hyderabad, India. Analysis indicated an increase in the frequencies of HLA DQ B1* 03 allele (P < 0.000) and HLA DR B1* 04 (P < 0.05) alleles in this group of patients when compared to the controls, whereas the frequency of DQB1* 05 was found to be decreased in patients' group compared to the controls (p < 0.01). To conclude, we report a positive correlation between DQ B1* 03 and DR B1* 04 and goitrous juvenile autoimmune hypothyroidism, whereas DQB1* 05 is observed to be negatively correlated with this thyroid dysfunction. Since the disease-susceptible HLA class II alleles appear to differ in various ethnic groups for some autoimmune diseases, the observed association from Indian series of patients holds significance.     

HLA-DR-associated genetic control of the type of leprosy in a population from Surinam

The relationship between HLA phenotype and leprosy classification was studied in 73 unrelated patients and 92 healthy controls from a mixed Negroid-Caucasoid population originating from Surinam, South America. Heterogeneity in the distribution of HLA-DR (but not A, B, and C) was detected between tuberculoid (TT^* + BT^*) leprosy and lepromatous (BL^* + LL^*) leprosy patients (p = 0.024). This heterogeneity appeared to be caused almost exclusively by DR3. Most significantly, the frequency of DR3 was increased among polar tuberculoid (TT) leprosy patients as compared to the rest of the patients (p = 0.0003). Compared with healthy controls the frequency of DR3 was increased among TT patients p = 0.0006), unchanged in BT patients, and decreased among lepromatous (BL + LL) patients (p = 0.027). These data indicate that in this population an DR3-associated factor controls the type of the disease that develops after infection with Mycobacterium leprae.     

Human leukocyte antigen class I and class II allele frequencies and HIV-1 infection associations in a Chinese cohort

China has one of the most rapidly spreading HIV-1 epidemics. To develop a vaccine targeted to specific human leukocyte antigen (HLA) epitopes in this population, allele distribution analysis is needed. We performed low-resolution class I and II HLA typing of a cohort of 393 subjects from mainland China using a polymerase chain reaction with sequence-specific primers (PCR-SSPs). We found 10 class I alleles present in more than 10% of the population: HLA-A*02, HLA-A*11, HLA-A*24, HLA-B*13, HLA-B*15, HLA-B*40, HLA-Cw*03, HLA-Cw*07, HLA-Cw*01, and HLA-Cw*06. Several class II alleles were found at high frequency (>or=10%): HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-DRB1*0701, HLA-DRB1*1501, HLA-DRB1*0401, HLA-DRB1*0901, HLA-DRB1*1201, HLA-DQB1*0601, HLA-DQB1*0301, HLA-DQB1*0201, HLA-DQB1*0501, and HLA-DQB*0303. We also estimated 2- and 3-locus haplotype frequencies. Because this cohort contained 280 HIV-1-seropositive and 113 HIV-1-seronegative individuals, we compared allele and haplotype frequencies between the infected and control groups to explore correlations between HLA antigens and susceptibility/resistance to HIV infection. The HLA-B*14 allele was only found in the HIV-1-seropositive group, and many 2-locus haplotypes were significantly overrepresented in this group: HLA-B*14/Cw*08, HLA-B*51/Cw*14, HLA-A*02/B*13, HLA-A*31/Cw*14, HLA-A*02/Cw*06, and the class II haplotype HLA-DRB1*1301/DQB1*0601. Alleles significantly increased in the HIV-1-seronegative controls were HLA-B*44, HLA-Cw*04, and HLA-DRB1*1402. Overrepresented 2-locus haplotypes in the control group were HLA-B*44/Cw*04, HLA-A*31/Cw*03, HLA-A*03/Cw*07, HLA-A*11/B*13, HLA-A*11/B*38, HLA-A*24/B*52, and HLA-A*11/Cw*01. The 3-locus haplotypes HLA-A*24/Cw*03/B*40 and HLA-A*02/B*15/DRB1*1201 were found to be increased significantly in the control group. These data contribute to the database of allele frequencies and associations with HIV infection in the Chinese population.     

HLA-A, -B, -C, -DR, -DQ typing in a population group of Senegal: distribution of HLA antigens and HLA-DRB1*13 and DRB1*11 subtyping by PCR using sequence-specific primers (PCR-SSP)

One-hundred-and sixteen Senegalese Serere were typed for HLA antigens and compared with other ethnic groups in Gambia. We did not find significant differences (Fisher's exact test; P0.01) in the HLA antigens distribution between the Serere and Mandinka groups in Senegal and the Serere, Mandinka and Wolof in The Gambia. The most common HLA haplotypes found (P0.01; Chi square with Yates' correction) were: A1, B8; A2, B51; A32, B44; A33, B58; A2, Cw2; A2, Cw4; A33, Cw3; A2, DR17; A10, DR10; B35, Cw4; B53, Cw6; B57, Cw3; B65, Cw8; B50, DR15; B52, DR4; Cw2, DR17; DR7, DQ2; DR18, DQ4. The HLA-DRB1*13 and DRB1*11 alleles were subtyped by PCR-SSP and the frequencies of these alleles in the studied population given. HLA-DRB1*1304 and DRB1102 were the most common alleles found respectively 15.0 and 18.5%     

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

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, A1 (pc less than 0.05) and DQw2 (pc less than 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.     

Persistence of hepatitis C virus in a white population: associations with human leukocyte antigen class 1

The aim of this study was to define novel associations between human leukocyte antigen (HLA) class 1 alleles and persistence or clearance of the hepatitis C virus (HCV) in a white population. All individuals in the study were seropositive for anti-HCV antibodies. Viral status was determined by the Roche HCV Amplicor test. HLA-A, -B, -C allelic group profile was molecularly defined by reverse line probe hybridization. The strongest individual allelic group associations with persistent HCV infection were HLA A*11 (p = 0.044) and Cw*04 (p = 0.006). However, only the HLA C*04 association survived correction for multiple comparisons. Further analysis of alleles in linkage with HLA Cw*04 revealed that the haplotype HLA A*11, Cw*04 was present in 11 individuals, 10 of whom were viremic (p = 0.05). No gene dosage effect was observed. No association between HLA class 1 allelic groups and aviremia and virus load was evident in this white population. HLA B*44 is associated with low virus load in human immunodeficiency virus disease, but this association was not evident in this HCV-infected population. Novel HLA class 1 alleles associated with persistence of HCV have been identified.