A sex-specific difference in homozygosity for HLA-DR53 in newborns.
Homozygosity for HLA-DR53 confers increased susceptibility to major forms of leukemia. In childhood leukemia, this influence is male-specific. Two separate studies have shown a male-specific increase in the homozoygosity rate for HLA-DR53 in healthy adults. This finding was attributed to possible preferential transmission of HLA-DR53 towards male offspring. If this is the case, the consequences of such a prenatal event should be evident in the newborn population. The present study investigated HLA-B and -DQA1 genotype frequencies in a sample of 134 newborns (73 boys, 61 girls) in Turkey. Restriction fragment length polymorphism (RFLP) analysis showed a homozygosity rate of 8.2 percent for HLA-DR53. Nine of 11 homozygotes were boys and the sex-specific rates were 12.3 percent vs 3.3 percent in boys and girls, respectively (p = 0.05). The DR53 homozygosity rate in males was higher than the expected rate (p = 0.02). These findings suggested a prenatal mechanism behind the excess of DR53 homozygotes in the male population. To maintain equilibrium, this excess seems to be eliminated postnatally. This model also explains how a deleterious genotype escapes natural selection.
Department of Hematology, University of Wales College of Medicine, Cardiff, U.K.
A
A
Sunguroğlu
D
D
Güç
T U
TU
Sipahi
M T
MT
Dorak
D005260:Female; D005787:Gene Frequency / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059845:HLA-DRB4 Chains; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D012641:Selection, Genetic; D012727:Sex Characteristics; D014421:Turkey
D015235:HLA-B Antigens; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen; D006684:HLA-DR Antigens; C050610:HLA-DR53; D059845:HLA-DRB4 Chains