Association of RANTES −403 G/A, −28 C/G and In1.1 T/C polymorphism with HIV‐1 transmission and progression among North Indians

Abstract

The relationships between host immune factors and HIV-1 disease progression are still in dispute. The RANTES SNPs exhibit distinct ethnic distribution and are associated with different effects on the course of HIV infection. Therefore, impact of RANTES gene polymorphism on HIV-1 transmission and progression needs to be evaluated. The RANTES genotypes were identified by PCR-RFLP method and confirmed by sequencing in HIV-1 seronegative (HSN; n=315), HIV-1 exposed seronegative (HES; n=47) and HIV-1 seropositive (HSP; n=196) patients classified into different clinical stages (i.e. Stages I, II, III). Fisher exact test was used for statistical analysis and Arlequin software for haplotype analysis. RANTES allele -403G, -28C and In1.1 T were the predominant allele in the subject studied. HSP group have higher frequency of RANTES In1.1 T allele compared with HSN (91.32% vs. 86.19%; P=0.013) and HES (91.32% vs. 78.72%; P=0.001). Higher frequency of RANTES In1.1 C allele in Stage III was observed, compared with Stage I (14.28% vs. 6.39%) and was significantly associated with high risk (P=0.047, OR=2.439, C.I.=1.061-5.609). Haplotype II (ACT) was significantly higher in HSP compared with HSN (9.69% vs. 1.58%) and associated with high risk (P<0.001, OR=6.655, C.I.=2.443-18.132). There were no significant differences in RANTES -403 A/G and -28 C/G genotype and allele distribution in all the groups compared. Our results implicate that RANTES In1.1 T allele and haplotype II (ACT) may be a risk factor for HIV-1 transmission while RANTES In1.1 C allele may be risk factor for disease progression among North Indians.

RANTES Gene Polymorphisms Associated with HIV-1 Infections in Kenyan Population

“…Our study confirms similar trends of distribution and lack of association of RANTES -403 and -28 genotypes with higher transmission rates [28]. …”

“…The most frequent of those polymorphic sites comprise -28C to G and -403G to A in the promoter region and In1.1 T/C in the first intron region of RANTES gene [28]. Usually, the two SNPs (28C/G and -403G/A) are always in complete linkage disequilibrium such that only three haplotypes are seen rather than the four that are theoretically possible [13, 16].…”

“…The study did not include other RANTES SNPs that have been associated with higher disease transmission risk like the RANTES In1.1 T allele [28]. …”

Host genes associated with HIV/AIDS: advances in gene discovery

“…Down-regulation of CCL5 levels by these regulatory SNPs are associated with HIV acquisition, progression to AIDS, and higher viral load in both Asian and European populations [28][30]. [31] [32] [33] [34]. These detrimental effects continue even after antiviral treatment [19].…”

Distribution of CC-chemokine receptor-5-∆32 allele among the tribal and caste population of Vidarbha region of Maharashtra state

“…[6] Majumder and Dey,[10] reported absence of CCR5-∆32 in various ethnic populations of India, both tribal and non-tribal, except for some populations of the northern and western regions where this allele may have been introduced by Caucasian gene flow. Although a few studies on chemokine, chemokine receptor, and DCSIGN exon 4 repeat number polymorphisms have been reported in north Indian (Aryan descent) HIV patients and healthy controls,[111213] there is a dearth of reports on the HIV patients with and without tuberculosis (TB) of South Indian (Dravidian descent) origin.…”