Associations of Chemokine Receptor Polymorphisms With HIV-1 Mother-to-Child Transmission in Sub-Saharan Africa: Possible Modulation of Genetic Effects by Antiretrovirals

Singh, Kumud K.; Hughes, Michael D.; Chen, Jie; Phiri, Kelesitse; Rousseau, Christine; Kuhn, Louise; Coutsoudis, Anna; Jackson, J. Brooks; Guay, Laura; Musoke, Philippa; Mmiro, Francis; Semba, Richard D.; Spector, Stephen A.

doi:10.1097/qai.0b013e318186eaa4

Cited by 25 publications

(27 citation statements)

References 33 publications

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“…CX3CR1 745G>A variation alone may not have a significant role in HIV transmission. These observations are supported by a study involving three sub-Saharan countries, South Africa, Uganda and Malawi, which also failed to observe any association between CX3CR1 745G>A variation and HIV infection in children born to antiretroviral therapynaïve mothers [28]. The findings of the above study [28] may have been distorted by the heterogeneous samples drawn from the three different countries involved.…”

Section: Chemokine Receptor Polymorphism and Their Association With Hsupporting

confidence: 55%

“…These observations are supported by a study involving three sub-Saharan countries, South Africa, Uganda and Malawi, which also failed to observe any association between CX3CR1 745G>A variation and HIV infection in children born to antiretroviral therapynaïve mothers [28]. The findings of the above study [28] may have been distorted by the heterogeneous samples drawn from the three different countries involved. In a separate study, this research group demonstrated differences in distribution of genetic variants among African populations; pooling samples from different countries in genetic association studies, therefore, may introduce bias [29].…”

Section: Chemokine Receptor Polymorphism and Their Association With Hsupporting

confidence: 55%

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CCR2, CX3CR1, RANTES and SDF1 genetic polymorphisms influence HIV infection in a Zimbabwean pediatric population

Mhandire

Duri

Kandawasvika

et al. 2014

J Infect Dev Ctries

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Introduction: There is growing evidence that polymorphisms in chemokine and chemokine receptor genes influence susceptibility to HIV infection and disease progression. However, not much is documented about the prevalence and effects of chemokine and chemokine receptor gene variations in the Zimbabwean population despite the high burden of HIV/AIDS in the country. This study therefore describes polymorphisms in CCR2, CX3CR1, SDF1 and RANTES genes in a Zimbabwean pediatric population and their effects on HIV infection in children born to HIV-infected mothers. Methodology: A total of 106 children between seven and nine years of age comprising 70 perinatally exposed to HIV (34 born infected [EI] and 36 born uninfected [EU]) and 36 unexposed and uninfected (UEUI) controls were recruited. Six allelic variants in four genes were genotyped using PCR-RFLP and sequencing. Results: Frequencies for minor alleles in the HIV uninfected groups (EU and UEUI) were CCR2 190A (16%), SDF1 801A (2%), CX3CR1 745A (9%), CX3CR1 839T (0%), RANTES In 1.1C (20%), and RANTES -403A (44%). There were significant differences between the EI and EU groups in the distribution of CCR2 190G/A genotype (15% versus 39%, respectively, p = 0.02) and CCR2 190G/A-CX3CR1 745G/G genotype combination (0% versus 33%, respectively, p = 0.002). Conclusions: Our findings suggest that chemokine and chemokine receptor gene variants seem to play an important role in the dynamics of HIV infection and could be used as drug or vaccine targets.

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Section: Chemokine Receptor Polymorphism and Their Association With Hsupporting

confidence: 55%

Section: Chemokine Receptor Polymorphism and Their Association With Hsupporting

confidence: 55%

CCR2, CX3CR1, RANTES and SDF1 genetic polymorphisms influence HIV infection in a Zimbabwean pediatric population

Mhandire

Duri

Kandawasvika

et al. 2014

J Infect Dev Ctries

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“…Genomic DNA extracted from dried blood spots using QIAamp DNA Mini Kit (Qiagen, Valencia, CA) was genotyped for CCR5-wt/Δ32, CCR5 -59029-G/A, CCR2-180 -G/A, SDF-1 -G/A, IL4-589-C/T, MCP-1-2518-A/G, MBL 2, APOE 2060-T/C and 2198-C/T (distinguishing ε2, ε3 and ε4 alleles), CCL3L2 copy number variants (CNVs), and CX 3 CR1 -745-G/A, -849-C/T polymorphisms using real-time PCR (LightCycler, Roche) as described previously [13, 20, 21]. These genetic variants were selected because each has previously been found to be associated with HIV-related disease progression and/or neurocognitive impairment.…”

Section: Methodsmentioning

confidence: 99%

APOE ε4 and MBL-2 O/O genotypes are associated with neurocognitive impairment in HIV-infected plasma donors

Spector

Singh²,

Gupta³

et al. 2010

Aids

Self Cite

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Background Host genetic factors are important determinants for risk of HIV-1 infection and disease progression. This study examined associations of host genetic variants and neurocognitive impairment in Chinese subjects infected through contaminated blood products. Methods 201 HIV-infected subjects from Anhui, China had neuropsychological (NP) tests at baseline and 12 months. DNA was genotyped for APOE ε2, ε3 and ε4 alleles, MBL2-A/O,CCR5-wt/Δ32, CCR5-59029-G/A, CCR2-180-G/A, SDF-1-G/A, IL4-589-C/T, MCP-1-2518-A/G, CX3CR1-745-G/A, -849-C/T polymorphisms and CCL3L1 copy number variants (CNVs) using real-time PCR. Univariate and multivariate analyses were performed. Results The cohort was 61% males, mean education: 5.5 years, AIDS diagnosis: 113(55%), on antiretrovirals: 114(56%), mean baseline CD4+ count: 349/mm3 and mean log10 RNA 4.09. At baseline, 37% had global NP impairment increasing to 44% after 12 months. Of 43 subjects with the APOE ε4 allele, 58% were cognitively impaired versus 31% without the ε4 allele (P=0.001, OR: 3.09; 95% CI: 1.54, 6.18). The mean GDS for ε4 positive participants on antiretrovirals for 12 months was 0.88 (0.55) versus 0.63 (.54) for ε4 negatives (P = 0.053, 95%CI: -0.004, 0.51). For MBL2, 52% of subjects with the O/O genotype declined in cognitive function over 12 months versus 23% with A/A (OR = 3.62. 95% CI: 1.46, 9.03; P=0.004). No associations were observed for the other genetic variants. Conclusions The APOE ε4 allele was associated with increased risk for cognitive deficits, while the MBL2 O/O genotype was associated with increased risk for progressive cognitive decline in Chinese subjects infected with HIV through contaminated blood products.

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“…In addition, variations in the use of antiretrovirals may also alter the effect of host genetics on HIV-1 transmission, as observed in a recent study of an HIV-1 mother-to-child transmission population administered preventive antiretrovirals. 30 These results further suggest that demographic or behavioral variations might play a role in the observed differences in HIV acquisition vulnerability, although no demographic or behavioral variations related to the CD4 C868T SNP have been found to date. 31 In summary, this study demonstrates a null association between the CD4 C868T genetic polymorphism and an individual's susceptibility to HIV-1 acquisition in a Chinese population.…”

Section: Discussionmentioning

confidence: 77%

The CD4 C868T Polymorphism and Its Correlation with HIV-1 Infection in a Chinese Population

Qin

et al. 2015

AIDS Research and Human Retroviruses

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Previous studies performed in Kenya have suggested that the C868T single nucleotide polymorphism (SNP) in CD4 increases the risk of HIV-1 acquisition; however, no relevant study has been conducted in China. To evaluate the influence of this SNP on risk of HIV-1 infection in a Chinese population, the CD4 genotype was determined by DNA sequencing in 101 HIV-1 patients and 102 healthy controls. No significant differences in the genotype and allele distributions of this polymorphism were observed among the patient and control groups. Additionally, binary logistic regression analyses adjusted by age and gender revealed that the C868T polymorphism was not associated with risk of HIV-1 infection. Furthermore, when analyses of genotype and allele frequencies were stratified by gender, similar nonsignificant results were found. Our study demonstrates a null association between the CD4 C868T polymorphism and an individual's susceptibility of HIV-1 acquisition in a Chinese population. Further studies are warranted to confirm these results.

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Associations of Chemokine Receptor Polymorphisms With HIV-1 Mother-to-Child Transmission in Sub-Saharan Africa: Possible Modulation of Genetic Effects by Antiretrovirals

Abstract: Background-HIV-1 mother-to-child transmission (MTCT) remains an important route of infection in sub-Saharan Africa.

Cited by 25 publications

References 33 publications

CCR2, CX3CR1, RANTES and SDF1 genetic polymorphisms influence HIV infection in a Zimbabwean pediatric population

CCR2, CX3CR1, RANTES and SDF1 genetic polymorphisms influence HIV infection in a Zimbabwean pediatric population

APOE ε4 and MBL-2 O/O genotypes are associated with neurocognitive impairment in HIV-infected plasma donors

The CD4 C868T Polymorphism and Its Correlation with HIV-1 Infection in a Chinese Population

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