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HLA class II haplotypes often contain a second expressed HLA-DRB locus tightly linked to the classical HLA-DRB1 locus on the haplotype, which can be either HLA-DRB3, -DRB4 or -DRB5. These encode the HLA-DR51, -DR52 or -DR53 supertypic specificities and mark the ancestral lineages. HLA-DRB3/B4/B5 heterozygote excess in Welsh male newborns has been reported, suggesting a possibility of male-specific major histocompatibility complex (MHC)-mediated prenatal selection. However, it has not been confirmed in newborns of other ethnic groups or in adult populations. We analyzed the HLA-DRB1 and HLA-DRB3/B4 B5 genes in Korean newborns and healthy adults to examine whether MHC-mediated prenatal or postnatal selection exists. A total of 1,038 newborns (cord blood registry, 516 males and 522 females) and 2,082 healthy adults (hematopoieti stem cell donor registry, 1,111 males and 971 females) were HLA typed. HLA DRB1/B3/B4/B5 DNA typing was performed using Dynal RELI HLA-DRB SSO Kit (Dyanl Biotech, Wirral, U.K.). Genotype frequencies and homozygosity and heterozygosity rates for DRB3/B4/B5 supertypic loci were compared between males and females in newborns and adults. There were no significant difference in the HLA-DRB3/B4/B5 homozygosity and heterozygosity rates between male and females in both newborns and adults. In the comparison between newborns and adults, homozygosity rate was significantly higher in newborn females than in adult females (31.0% vs 25.0%, p = 0.01). Whether there is an age-related change from newborns toward adults has not been well studied in other populations, and further studies are warranted. In conclusion, male-specific heterozygosity excess reported in Welsh newborns has not been observed in Korean population, and there might be some ethnic differences in the gender-specific prenatal selection events. [ABSTRACT FROM AUTHOR]