Variation in human β‐defensin genes: new insights from a multi‐population study

Summary Human β‐defensin 2 ( hBD ‐2) and hBD ‐3, encoded by DEFB4 and DEFB103A , respectively, have shown anti‐HIV activity, and both genes exhibit copy number variation (CNV). Although the role of hBD ‐1, encoded by DEFB1 , in HIV‐1 infection is less clear, single nucleotide polymorphisms (SNPs) in DEFB1 may influence viral loads and disease progression. We examined the distribution of DEFB1 SNPs and DEFB4 / 103A CNV, and the relationship between DEFB1 SNPs and DEFB4 / 103A CNV using samples from two HIV/AIDS cohorts from the United States ( n  = 150) and five diverse populations from the Coriell Cell Repositories ( n  = 46). We determined the frequencies of 10 SNPs in DEFB1 using a post‐PCR, oligonucleotide ligation detection reaction–fluorescent microsphere assay, and CNV in DEFB4 / 103A by real‐time quantitative PCR. There were noticeable differences in the frequencies of DEFB1 SNP alleles and haplotypes among various racial/ethnic groups. The DEFB4/103A copy numbers varied from 2 to 8 (median, 4), and there was a significant difference between the copy numbers of self‐identified whites and blacks in the US cohorts (Mann–Whitney U‐ test P  =   0.04). A significant difference was observed in the distribution of DEFB4/103A CNV among DEFB1 ‐52G/A and ‐390T/A genotypes (Kruskal–Wallis P  =   0.017 and 0.026, respectively), while not in the distribution of DEFB4/103A CNV among ‐52G/A_‐44C/G_‐20G/A diplotypes. These observations provide additional insights for further investigating the complex interplay between β‐defensin genetic polymorphisms and susceptibility to, or the progression or severity of, HIV infection/disease.