title: Variation in human β-defensin genes: new insights from a multi-population study.
abstract: 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.
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: R K
authors.initials: RK
authors.lastname: Mehlotra
authors.forename: P A
authors.initials: PA
authors.lastname: Zimmerman
authors.forename: A
authors.initials: A
authors.lastname: Weinberg
authors.forename: R J
authors.initials: RJ
authors.lastname: Jurevic
mesh_terms: D015331:Cohort Studies; D056915:DNA Copy Number Variations / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D023083:beta-Defensins / Q000235:genetics*
chemical_list: C406407:DEFB1 protein, human; C422950:DEFB103A protein, human; C106641:DEFB4A protein, human; D023083:beta-Defensins