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JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e3182172d03
Letter to the Editor

CCR5 Chemokine Receptor Polymorphism in Patients With HIV-1 From Western India

Shankarkumar, Aruna PhD; Shankarkumar, Umapathy PhD; Ghosh, Kanjaksha MD

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National Institute of Immunohaematology, KEM Hospital, Parel, Mumbai, India

To the Editors:

AIDS is a set of symptoms and infections resulting from the damage to the human immune system caused by HIV. The rate of disease progression depends on viral characteristics and host factors. Entry of HIV-1 into target cells requires both CD4 and chemokine receptors. A 32-nucleotide deletion (Δ32) within the β-chemokine CCR5 gene has been described in HIV-1 subjects who remain uninfected. We investigated the frequency of Δ32 deletion in CCR5 among HIV-1-infected patients and normal uninfected healthy individuals belonging to the same ethnic background. A total of 251 samples comprised 161 patients with HIV-1 and 90 normal healthy individuals from the same ethnic group. Genomic DNA from patients and control subjects was extracted and amplified for CCR5 gene segment using polymerase chain reaction. Amplified products were analyzed on 12% acrylamide gel, which yielded an 189-bp fragment for the wild-type allele and 157-bp fragment for the deleted (mutant) allele. Our results revealed patients with HIV-1 were homozygotous for ccr5Δ32 deletion (6.21%) and heterozygous for ccr5Δ32 deletion (0.67%) compared with 6.66% and 0%, respectively, in control subjects (Table 1). Genetic susceptibility to HIV infection has proven to be influenced by chemokine receptor gene polymorphisms culturing on chomosome 3p21. The chemokine receptors CCR2V64I, CCR5-Delta 32, CCR5 m303, CXCR4,(-2459)A CCR5, G190A CCR2,744A, CX3CR1, C838T, and SDF1-3A have been implicated in HIV. Homozygocity for the CCR5 (delta32/delta32) gene is associated with strong resistance against HIV infection. Hetrozygocity for CCR5 (delta32/wt) is associated with protection of HIV disease progression. Global survey for this genotype has revealed that 13% of whites have this mutant allele, whereas in Africans, Eurasians, and Indians, the allele ranges from 5% to 10%.1 The CCR5 delta is a heterozygous deletion in Slovakian patients with HIV-1 (15.4%)2 and heterozygous deletion in white patients with HIV ( 17.5%) and in Polish patients with HIV-1 (16.1%).1 The CCR5 delta32 homozygous deletion is reported in a single German seroconverter,3 not identified in North Indians,4 but identified (6.21%) in our present investigation from Western Indians. Studies revealed that a second mutation in CCR5 that is a single base pair mutation, m303, introduces a stop codon that prevents cell surface expression of a functional CCR5 receptor. A recent study reported the CCR5Delta32 (2.8%) and CCR5m303 (0%) allele polymorphisms among Bahraini population.5 Considering the ethnicity of the Indian subcontinent, CCR5 gene studies in patients with HIV-1 from other parts of India will give us more information. Our study shows that the CCR5 allele frequency varies in different ethnic groups and 7.84% of the patients with HIV-1 have not been protected although they have the presence of the homo- or heterozygous ccr532bp deletion.

Table 1
Table 1
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Aruna Shankarkumar, PhD

Umapathy Shankarkumar, PhD

Kanjaksha Ghosh, MD

National Institute of Immunohaematology, KEM Hospital, Parel, Mumbai, India

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REFERENCES

1. Parczewski M, Leszezszyn-Pynka M, Kaczmarczyk M, et al. Sequence variants of chemokine receptor genes and susceptibility to HIV-1 infection J Appl Genet. 2009;50:159-166.

2. Takacova M, Nogava P, Habekova M, et al. Prevalence of 32 bp deletion in the gene for human immunodeficiency virus1 co-receptor ccr5 in Slovak population. Acta Virol. 2008;52:261-264.

3. Oh DY, Jessen H, Kucherer C, et al. CCR5Delta32 genotypes in German HIV-1 seroconverter cohort and report of HIV-1 infection in a CCR5delta 32 homozygous individual. PLoS One. 2008;3:e2747.

4. Kaur G, Singh P, Rapthap CC, et al. Polymorphism in the CCR5 gene promoter and HIV-1 infection in North Indians. Hum Immunol. 2007;68:454-461.

5. Salem AH, Farid E, Fadel R, et al. Distribution of four HIV type 1- resistance polymorphisms (CCR5-Delta32, CCR5-m3o3, CCR2-64I and SDF-3′A) in Bahraini population. AIDS Res Hum Retroviruses. 2009;25:973-977.

© 2011 Lippincott Williams & Wilkins, Inc.

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