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Abstract
Background:
In the search for susceptibility genes responsible for leukemia, genetic studies involving HLA association have been in progress extensively since the first report on its effect on the disease. Here we investigated the genetic associations of different leukemias with 4 autosomal mHags, HA-1, -2, -8 and HB-1. In particular, HB-1 is one of the leukemia-associated minor histocompatibility antigens (mHags) that is significantly expressed by Epstein-Barr virus-transformed- and tumor cells of all B lineage acute lymphoblastic leukemia (ALL).
Methods:
A simultaneous genotyping method using PCR sequence-specific primers against HA-1, -2, -8 and HB-1 was developed, and their allelic frequencies in 139 healthy controls and 36 leukemia patients were observed. To compare genotype, phenotype, and gene frequencies of mHags with healthy controls, leukemia patients were classified into sub groups of ALL, acute myeloid leukemia (AML), and chronic myeloid leukemia (CML).
Results:
The genotype frequencies of HA-1, -2 and -8 were not significantly different from healthy controls in every group of leukemia patients. However, the HB-1 H genotype was significantly increased in leukemia patients (P=0.03, OR=1.82, CI=1.08～3.06), particularly in AML (P=0.01, OR=2.4, CI=1.21～ 4.76) as compared with healthy controls.
Conclusion:
Our results suggested that the genotype of HB-1 H may be associated with leukemia, particularly with AML. In further study, it is necessary to confirm the association of HB-1 with other leukemias in a larger group of patients, and to identify the underlying mechanism of HB-1 responsible for the occurrence of leukemia.
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Fig 1.
Genotyping of HA-1, -2, -8 and HB-1 by PCR-SSP. Lane 1: H type for HA-1, lane 2: R type for HA-1, lane 3: V type for HA-2, lane 4: M type for HA-2, lane 5: R type for HA-8, lane 6: P type for HA-8, lane 7: H type for HB-1, lane 8: Y type for HB-1. Each type of mHags HA-1, -2, -8 and HB-1 of the three samples was as follows; sample 1: HH (HA-1), VM (HA-2), PP (HA-8), HH (HB-1); sample 2: RR (HA-1), VM (HA-2), RP (HA-8), YY (HB-1); sample 3: HR (HA-1), VV (HA-2), RR, (HA-8), HY (HB-1).
Fig. 2
Allelic frequencies of HA-1, -2, -8 and HB-1 in healthy controls (n=139) and patients with leukemia (n=36) in the Korea.
Table 1.
Primer sets for genotyping of HA-1, HA-2, HA-8, and HB-1
Table 2.
Genotype and phenotype frequencies of HA-1 in healthy controls and patients with leukemia in Korea
Table 3.
Genotype and phenotype frequencies of HA-2 in healthy controls and patients with leukemia in Korea
Table 4.
Genotype and phenotype frequencies of HA-8 in healthy controls and patients with leukemia in Korea
Table 5.
Genotype and phenotype frequencies of HB-1 in healthy controls and patients with leukemia in Korea
| Genotype frequency n (%) | ||||||
|---|---|---|---|---|---|---|
| Locus | Healthy controls | Leukemia patients | ||||
| (n=139) | Total (n=36) | ALL (n=12) | AML (n=20) | CML (n=4) | ||
| HB-1 | HH | 31 (22.3) | 16 (44.4)∗ | 5 (41.7) | 10 (50)∥ | 1 (25) |
| YH | 67 (48.2) | 12 (33.3) | 2 (16.6) | 7 (35) | 3 (75) | |
| YY | 41 (29.5) | 8 (22.3) | 5 (41.7) | 3 (15) | 0 (0) | |
| H | 98 | 28 | 7 | 17 | 4 | |
| Y | 108 | 20† | 7 | 10¶ | 3 | |
| Gene frequency n (%) | ||||||
| H | 129 (46.4) | 44 (61.1)‡ | 12 (50) | 27 (67.5)∗∗ | 5 (62.5) | |
| Y | 149 (53.6) | 28 (38.9)§ | 12 (50) | 13 (32.5)†† | 3 (37.5) | |
∗P-value was calculated by chi-square tests of total leukemia patients versus healthy controls (P=0.008, OR=2.8, CI=1.32～ 5.91);
† P-value was calculated by chi-square tests of total leukemia patients versus healthy controls (P=0.008, OR=0.36, CI=0.17～0.76);
‡ P-value was calculated by chi-square tests of total leukemia patients versus healthy controls (P=0.03, OR=1.82, CI=1.08～3.06);
§ P-value was calculated by chi-square tests of total leukemia patients versus healthy controls (P=0.03, OR=0.56, CI=0.33～0.93);
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