Polymorphic variants in DC-SIGN, DC-SIGNR and SDF-1 in high risk seronegative and HIV-1 patients in Northern Asian Indians.
A single nucleotide polymorphism (SNP) in SDF-1, the natural ligand for the HIV-1 coreceptor CXCR4, is implicated to have protective effects against HIV-1 infection. Dendritic cells are the first to encounter HIV-1 at mucosal sites and virus binding occurs via receptors known as DC-SIGN. Variations in the number of repeats in the neck region of DC-SIGN and DC-SIGNR are reported to possibly influence host susceptibility to HIV-1 infection. We examined the SNP of SDF1-3'A by PCR-restriction fragment length polymorphism (RFLP) and repeat region polymorphisms in DC-SIGN and DC SIGNR by PCR in healthy HIV seronegative individuals, high risk STD patients seronegative for HIV, and HIV-1 seropositive patients from northern India. The detected polymorphisms were confirmed by cloning and sequencing. The genotypic frequency of SDF1-3'A/SDF1-3'A in the 100 HIV-seronegative healthy individuals, 150 HIV seronegative STD patients, and 100 HIV-1 seropositive patients were 4%, 18% and 7%, respectively. A significantly higher frequency of SDF1-3'A/SDF1-3'A was observed in high risk STD patients as compared to HIV seropositive (p=0.014) and healthy HIV-1 seronegative tested individuals (p=0.001), suggesting a protective role of SDF1-3'A in HIV-1 infection. DC-SIGN polymorphism was rare and genotype 7/7 was predominant in all groups studied. DC-SIGNR was highly polymorphic and 11 genotypes were observed among the different study groups. The precise role of the polymorphic variants of DC-SIGNR needs to be elucidated in the population.
Chaudhary
Omkar
O
Department of Biochemistry, Room No. 3002, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India. omkar1519@yahoo.co.in
Rajsekar
Kavitha
K
Ahmed
Imran
I
Verma
Romsha
R
Bala
Manju
M
Bhasin
Rama
R
Luthra
Kalpana
K
D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D054377:Chemokine CXCL12 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics* / Q000821:virology; D018023:HIV Seronegativity / Q000235:genetics; D015497:HIV-1; D006801:Humans; D007194:India / Q000453:epidemiology; D037181:Lectins, C-Type / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011956:Receptors, Cell Surface / Q000235:genetics*; D012306:Risk; D012749:Sexually Transmitted Diseases / Q000235:genetics; D055815:Young Adult; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D054377:Chemokine CXCL12; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C433029:CLEC4M protein, human; C515255:CXCL12 protein, human