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Table 1. Childhood Acute Lymphoblastic Leukaemia (ALL) and HLA-DRB4*01

Samples: 114 patients with childhood ALL diagnosed in the last 10 years in Cardiff and 325 cord blood samples obtained from babies born in Cardiff over a 12 months period.

There was no change in the allele frequency of HLA-DRB4*01 (heterozygous and homozygous genotypes together) between patients and controls:

All patients (66/114=57.9%) vs all newborns (174/325=53.5%); p=0.49

Male patients with ALL (41/61=67.2%) vs male newborns (77/150=51.3%); p=0.05

Homozygosity rates for HLA-DRB4*01:

All patients (24/114=21.1%) vs all newborns (27/325=8.3%); p=0.0005; OR=2.9

Male patients (20/61=32.8%) vs male newborns (6/150=4.0%); p=0.00000003; OR=11.7 (95% CI= 4.9 to 28.0)

Male patients with common ALL (15/40=37.5%) vs male newborns (4.0%); p=0.000002 [Fisher]; OR=14.4 (95% CI=5.8 to 35.9)

Male patients with ALL (32.8%) vs healthy adult males (624/4396=14.2%); p=0.00009

Female patients (3/51=5.9%) vs female newborns (21/175=12.0%); p=0.30 [Fisher]

Female patients with common ALL (3/37=8.1%) vs female newborns (12.0%); p=0.35 [Fisher]

The following comparisons were made to compare our data to that of a recent British study which stated that the DQA1*0101-DQB1*0501 haplotype was significantly more frequent in males with c-ALL than male controls (RR=9.48; p<0.001 or OR= 3.73) [Taylor GM et al.]. This haplotype corresponds to HLA-DRB1*01 in our study:

Male patients with common ALL (n=40) compared to male newborns (n=150):

HLA-DRB1*01 gene frequency: 28.8% vs 22.7% (p=0.32)

HLA-DRB1*01 presence (inferred antigen frequency): 52.5% vs 44.7% (p=0.48)

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Table 2. Healthy new-borns and HLA-DRB4*01

Sample: 325 cord blood samples from babies born in Cardiff from February 1997 until March 1998 without any selection (150 males and 175 females as confirmed by Y-chromosome-specific PCR analysis).

Gene frequency for HLA-DRB4*01= (201/650) 30.92%

Expected homozygosity rate (for both sexes) according to Hardy-Weinberg equilibrium= 9.56% (95% CI=6.36 to 12/76)

Observed homozygosity rates:

Whole group: 27/325 (8.3%) [lower than the adult homozygosity rate=1389/10,418=13.33%; p=0.01]

Boys: 6/150 (4.0%) [lower than the expected homozygosity rate (9.56%), p=0.02; rate in newborn girls (12.0%), p=0.016; rate in healthy adult males (624/4396=14.2%), p=0.0006]

Girls: 21/175 (12.0%) [no significant change from the expected rate (9.56%) or the rate in healthy adult females (765/6022=12.7%)].

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Table 3. Healthy Adults and HLA-DRB4*01

Sample: 800 healthy adults from the Welsh Bone Marrow Donor Registry.

Findings: Significant changes are restricted to the comparisons between males 18-25yr (n=70) and 26-45yr (n=258) [in females 18-25yr (n=116) and 26-45yr (n=356), there is no significant change in the corresponding frequencies]

(all of the following comparisons are for males in the two age groups)

Homozygosity rate for HLA-DRB4*01 :

(gene frequency=0.3388; expected homozygosity rate=11.48%)

20.00% vs 9.69 % p=0.03

20.00% vs exp (11.48%) p=0.025

Homozygosity for HSP70-L:DRB4*01:

(Delta=0.0305, p=0.09; haplotype frequency=25.4%; expected homozygosity rate=6.45%)

14.29% vs 5.43% p=0.02

14.29% vs exp (6.45%) p=0.008

Homozygosity for HLA-Bw4:DRB4*01:

(Delta=0.0552, p=0.00007; haplotype frequency=18.99%; expected homozygosity rate=3.61%)

8.57% vs 1.16% p=0.004

8.57 vs exp (3.61%) p=0.03

[total homozygosity 2.38% vs exp (3.61%) p=0.06]

Homozygosity for HLA-Bw4:HSP70-L:DRB4*01:

7.14% vs 0.39% p=0.001

Homozygosity for HLA-Bw4:HSP-L:

(Delta=0.0472, p=0.006; haplotype frequency=30.96%; expected homozygosity rate=9.58%)

18.42% vs 7.09% p=0.08

18.42% vs exp (9.58%) p=0.01

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