The Hodgkin’s lymphoma disease (HD) is a common malignant neoplasm with germinal centre B-cell origin. It has been suggested that the HLA class I and class II regions have susceptibility effects on HD. In different ethnic groups, different HLA class I and class II alleles affect HD. As a result, there is no consensus which of the different HLA alleles confers susceptibility to HD. In this study, we aimed to ascertain the role of HLA class I and class II alleles in association with Hodgkin’s lymphoma in Iranian patients. We performed a case-control genotyping study in 85 Iranian HD patients which were selected from the Bone Marrow Transplantation Department of Taleghani Hospital and 150 controls using the SSP-PCR. Our results demonstrated that the
The Hodgkin’s lymphoma disease (HD) is a common malignant neoplasm of germinal centre B-cell origin which is histopathologically characterized by the existence of very large Hodgkin Reed-Sternberg cell (HRS) [
Eighty-five Iranian patients (mean age of
Genomic DNA from peripheral blood samples was isolated by applying salting out method. The HLA typing was carried out at the Tehran Medical Genetics Laboratory. HLA-A, HLA-B, HLA-DRB1 genotyping was performed based on SSP-PCR by HLA-READY GENE ABDR Kit (Inno-Train Diagnostic GmbH, Germany) according to the manufacturer’s recommendation. The electrophoresis using 2% agarose gel was applied to amplified PCR products.
Comparisons between the various HLA-A, HLA-B, and HLA-DRB alleles of patients with HD and controls were made using the chi-square and Fisher’s exact tests. All the analyses were done using SPSS version 18.0 for windows software. The
Distributions of sex and age of HD patients and controls are summarized in Table
Distributions of sex and age of HD patients and control group.
Variables | HD patients | Controls |
---|---|---|
Female/Male (no. (%)) | 37/48 (43/57%) | 59/91 (39/61%) |
Age (mean ± SD, years) |
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Age range (years) | 14–49 | 15–53 |
The allele frequencies of HLA-A, HLA-B, HLA-DRB1 in HD patients and control groups.
Alleles | HD patients |
Controls |
|
PC valueb | OR (95% CI)c |
---|---|---|---|---|---|
HLA-A*01 | 15 (9%) | 30 (10%) | 0.67 | >0.999 | 0.871 (0.361–2.098) |
HLA-A*02 | 36 (21%) | 63 (21%) | 0.96 | >0.999 | 1.011 (0.542–1.885) |
HLA-A*03 | 20 (12%) | 57 (19%) | 0.04 | 0.546 | 0.568 (0.27–1.192) |
HLA-A*11 | 17 (10%) | 27 (9%) | 0.72 | >0.999 | 1.12 (0.472–2.654) |
HLA-A*23 | 5 (3%) | 9 (3%) | 0.97 | >0.999 | 0.98 (0.218–4.394) |
HLA-A*24 | 36 (21%) | 51 (17%) | 0.26 | >0.999 | 1.31 (0.688–2.491) |
HLA-A*26 | 3 (2%) | 15 (5%) | 0.07 | >0.999 | 0.341 (0.062–1.858) |
HLA-A*29 | 5 (3%) | 9 (3%) | 0.97 | >0.999 | 0.98 (0.218–4.394) |
HLA-A*30 | 7 (4%) | 12 (4%) | 0.95 | >0.999 | 1.03 (0.284–3.729) |
HLA-A*31 | 5 (3%) | 12 (4%) | 0.55 | >0.999 | 0.727 (0.173–3.050) |
HLA-A*32 | 5 (3%) | 6 (2%) | 0.51 | >0.999 | 1.48 (0.291–7.517) |
HLA-A*33 | 6 (4%) | 6 (2%) | 0.31 | >0.999 | 1.79 (0.379–8.447) |
HLA-A*68 | 10 (6%) | 3 (1%) | 0.002 |
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HLA-B*07 | 7 (4%) | 15 (5%) | 0.66 | >0.999 | 0.816 (0.197–3.37) |
HLA-B*08 | 2 (1%) | 12 (4%) | 0.08 | >0.999 | 0.286 (0.027–2.947) |
HLA-B*13 | 2 (1%) | 9 (3%) | 0.20 | >0.999 | 0.38 (0.034–4.133) |
HLA-B*14 | 2 (1%) | 9 (3%) | 0.20 | >0.999 | 0.38 (0.034–4.133) |
HLA-B*15 | 7 (4%) | 9 (3%) | 0.52 | >0.999 | 1.38 (0.291–6.537) |
HLA-B*18 | 5 (3%) | 12 (4%) | 0.55 | >0.999 | 0.72 (0.139–3.71) |
HLA-B*27 | 5 (3%) | 8 (3%) | 0.86 | >0.999 | 1.1 (0.190–6.345) |
HLA-B*35 | 34 (20%) | 53 (18%) | 0.53 | >0.999 | 1.16 (0.553–2.431) |
HLA-B*38 | 10 (6%) | 16 (5%) | 0.80 | >0.999 | 1.1 (0.312–3.868) |
HLA-B*39 | 7 (4%) | 9 (3%) | 0.52 | >0.999 | 1.38 (0.291–6.537) |
HLA-B*40 | 2 (1%) | 6 (2%) | 0.50 | >0.999 | 0.583 (0.048–7.04) |
HLA-B*41 | 2 (1%) | 9 (3%) | 0.20 | >0.999 | 0.385 (0.035–4.188) |
HLA-B*44 | 10 (6%) | 28 (9%) | 0.18 | >0.999 | 0.607 (0.190–1.929) |
HLA-B*48 | 2 (1%) | 6 (2%) | 0.50 | >0.999 | 0.583 (0.048–7.04) |
HLA-B*49 | 3 (2%) | 12 (4%) | 0.18 | >0.999 | 0.431 (0.059–3.115) |
HLA-B*50 | 3 (2%) | 15 (5%) | 0.07 | >0.999 | 0.34 (0.048–2.363) |
HLA-B*51 | 54 (32%) | 42 (14%) | 0.000003 |
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HLA-B*52 | 5 (3%) | 12 (4%) | 0.55 | >0.999 | 0.72 (0.139–3.71) |
HLA-B*54 | 2 (1%) | 0 (0%) | 0.25 | >0.999 | 2.78 (0.022–337.713) |
HLA-B*55 | 2 (1%) | 6 (2%) | 0.50 | >0.999 | 0.583 (0.048–7.04) |
HLA-B*57 | 2 (1%) | 3 (1%) | 0.85 | >0.999 | 1.17 (0.072–18.886) |
HLA-B*58 | 2 (1%) | 9 (3%) | 0.20 | >0.999 | 0.38 (0.034–4.133) |
HLA-DRB1*01 | 8 (5%) | 12 (4%) | 0.71 | >0.999 | 1.18 (0.339–4.099) |
HLA-DRB1*03 | 12 (7%) | 30 (10%) | 0.28 | >0.999 | 0.68 (0.261–1.768) |
HLA-DRB1*04 | 9 (5%) | 15 (5%) | 0.88 | >0.999 | 1.06 (0.333–3.369) |
HLA-DRB1*07 | 7 (4%) | 30 (10%) | 0.02 | 0.299 | 0.387 (0.122–1.21) |
HLA-DRB1*08 | 0 (0%) | 3 (1%) | 0.99 | >0.999 | 0.58 (0.0001–2918.205) |
HLA-DRB1*09 | 2 (1%) | 3 (1%) | 0.99 | >0.999 | 1.17 (0.102–13.374) |
HLA-DRB1*10 | 10 (6%) | 15 (5%) | 0.68 | >0.999 | 1.18 (0.384–3.624) |
HLA-DRB1*11 | 70 (41%) | 120 (40%) | 0.80 | >0.999 | 1.05 (0.571–1.928) |
HLA-DRB1*12 | 3 (2%) | 0 (0%) | 0.13 | >0.999 | 5.38 (0.001–27068.86) |
HLA-DRB1*13 | 12 (7%) | 30 (10%) | 0.28 | >0.999 | 0.68 (0.261–1.768) |
HLA-DRB1*14 | 10 (6%) | 21 (7%) | 0.63 | >0.999 | 0.83 (0.287–2.4) |
HLA-DRB1*15 | 24 (14%) | 9 (3%) | 0.000004 |
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HLA-DRB1*16 | 3 (2%) | 12 (4%) | 0.18 | >0.999 | 0.431 (0.075–2.444) |
The significant
HD is one of the multifactorial and heterogeneous malignancies of the immune system. In 1997, Ferraris et al. calculated that around 4.5% of HD was familial HD [
Our study indicates that, the
The susceptible and protective alleles or haplotypes in HD.
Susceptible and protective alleles or haplotypes | Study |
---|---|
Susceptible allele: HLA-B18 | Amiel 1967, Svejgaard et al., 1975, Bjorkholm et al., 1975, [ |
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Susceptible haplotype: DRB1*15:01-DQA1*01:02-DQB1*06:02 |
Klitz et al., 1994, [ |
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Susceptible allele: HLA-DRB1*15:01 |
Taylor et al., 1996, [ |
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Susceptible haplotype: DRB1*15:01-DQA1*01:02-DQB1*06:02 | Harty et al., 2002, [ |
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Susceptible alleles: HLA-DRB1*04:03 and HLA-DRB1*12:02 | Al-Tonbary et al., 2004 [ |
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Susceptible allele: HLA-DRB1*15:01 |
Moutsianas et al., 2011, [ |
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Susceptible alleles: HLA-A*68, HLA-B*51 and HLA-DRB1*15 | Present study |
The above descriptions demonstrated that there were differences in susceptible or protective alleles of HLA genes between populations. These differences may be resulting from their ancestries or the small sample size. In this study, we showed susceptible alleles in Iranian HD patients. Meta-analysis of results among populations, study on large sample size (especially on antigen binding groove), and more and precise studies in this field are necessary to clear the causes exact susceptible or protective alleles of HLA gene in HD.
In conclusion, the
The authors declare that there is no conflict of interests regarding the publication of this paper.