Risk for HIV-1 infection is not associated with repeat-region polymorphism in the DC-SIGN neck domain and novel genetic DC-SIGN variants among North Indians.
BACKGROUND
Several genetic factors have been related to HIV-1 resistance, the homozygosity for a mutation in CCR5 gene (CCR5Delta 32 allele) is presently considered the most relevant one. The C-type lectin, DC-SIGN efficiently binds and transmits HIV-1 to susceptible cell in trans thereby augmenting the infection. A potential association of the DC-SIGN neck domain repeats polymorphism and risk of HIV-1 infection is currently under debate.


METHODS
Genetic risk association study was conducted in HIV-1 exposed seronegative (HES; n=50) individuals, HIV-1 seronegative (HSN; n=314) healthy control and HIV-1 infected seropositive patients (HSP; n=190) for polymorphism in neck domain of DC-SIGN gene. The DC-SIGN genotypes were identified by PCR from DNA extracted from peripheral blood and confirmed by sequencing. Fisher exact or chi(2) test was used for statistical analysis.


RESULTS
One HSN and HSP individual who were heterozygous (7/8) with respect to DC-SIGN repeat regions were found. The DC-SIGN neck repeat polymorphism among North Indian individuals was not associated with susceptibility to HIV-1 infection. Furthermore, inheritance study of heterozygous mutation (7/8) in HSN individual's family showed that one parent, two brothers, one sister and one daughter were heterozygous (7/8) for DC-SIGN mutant allele. Sequence analyses of DC-SIGN exon 4 repeat region of randomly selected 25 North Indian individuals from HSP, HSN and HES revealed four conserved intronic mutations. These mutations were at nucleotide position 1283, 1306, 1308 upstream and 1906 downstream of the DC-SIGN exon 4 repeat region when compared with the wild type sequence (NCBI Acc. No. AF209479).


CONCLUSIONS
The polymorphism in DC-SIGN neck repeats region was rare and not associated with HIV-1 susceptibility among North Indians. Sequencing analysis of DC-SIGN gene confirmed four novel genetic variants in intronic region flanking exon 4 coding region.
Rathore
Anurag
A
Department of Microbiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebarelli Road, Lucknow, India.
Chatterjee
Animesh
A
Sood
Vikas
V
Khan
Sohrab Z
SZ
Banerjea
Akhil C
AC
Yamamoto
Naohiko
N
Dhole
Tapan N
TN
D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D015497:HIV-1; D006801:Humans; D007194:India / Q000453:epidemiology; D037181:Lectins, C-Type / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics*; D016415:Sequence Alignment; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin