Role of Homozygous DC-SIGNR 5/5 Tandem Repeat Polymorphism in HIV-1 Exposed Seronegative North Indian Individuals

• DOI: 10.1007/s10875-007-9131-x
• Publication Date: 2007-09-17T19:05:40Z
• Authors: Anurag Rathore; Animesh Chatterjee; P. Sivarama; Naohiko Yamamoto; Tapan N. Dhole
• Keywords: Adult; Male; Heterozygote; 0303 health sciences; Polymorphism, Genetic; Genotype; Homozygote; HIV Infections; Receptors, Cell Surface; Dendritic Cells; Middle Aged; Article; 3. Good health; 03 medical and health sciences; Gene Frequency; Tandem Repeat Sequences; HIV-1; Humans; Female; Genetic Predisposition to Disease; Lectins, C-Type; Cell Adhesion Molecules; Alleles; Aged

Despite multiple sexual exposures to HIV-1 virus, some individuals remain HIV-1 seronegative. Although several genetic factors have been related to HIV-1 resistance, the homozygosity for a mutation in CCR5 gene (the 32-bp deletion, i.e., CCR5-Delta32 allele) is presently considered the most relevant one. The C-type lectins, DC-SIGN (present on dendritic cells and macrophages) and DC-SIGNR (present on endothelial cells in liver and lymph nodes) efficiently bind and transmit HIV-1 to susceptible cell in trans, thereby augmenting the infection. A potential association of the DC-SIGN and DC-SIGNR neck domain repeat polymorphism and risk of HIV-1 infection is currently under debate. To determine the influence of host genetic factors on HIV-1 resistance, we conducted genetic risk association study in HIV-1-exposed seronegative (n = 47) individuals, HIV-1 seronegative (n = 262) healthy control, and HIV-1-infected seropositive patients (n = 168) for polymorphism in neck domain of DC-SIGN and DC-SIGNR genes. The DC-SIGN and DC-SIGNR genotypes were identified by polymerase chain reaction method in DNA extracted from peripheral blood and confirmed by sequencing. Fisher exact or chi (2) test was used for static analysis. DC-SIGN genotype and allele distribution was fairly similar in HIV-1-exposed seronegative, HIV-1 seropositive, and HIV-1 seronegative control. There was no statistical significance in the differences in the distribution of DC-SIGN genotypes. A total of 13 genotypes were found in DC-SIGNR neck repeat region polymorphism. Among all the genotypes, only 5/5 homozygous showed significant reduced risk of HIV-1 infection in HIV-1-exposed seronegative individuals (p = 0.009). A unique genotype 8/5 heterozygous was also found in HIV-1 seropositive individual, which is not reported elsewhere.