Limits...
Analysis of Social and Genetic Factors Influencing Heterosexual Transmission of HIV within Serodiscordant Couples in the Henan Cohort.

Zhu Q, Zhu P, Zhang Y, Li J, Ma X, Li N, Wang Q, Xue X, Luo L, Li Z, Ring HZ, Ring BZ, Su L - PLoS ONE (2015)

Bottom Line: There is considerable variability between individuals in susceptibility to infection by human immunodeficiency virus (HIV).We found that anti-retroviral therapy, education level, and condom use were the most significant factors in determining likelihood of HIV transmission in this study.Mixed effects models showed that these genetic variants both retained significance when assessed with either treatment or condom use.

View Article: PubMed Central - PubMed

Affiliation: Institute for AIDS/STD Prevention and Control, Henan Center for Disease Prevention and Control, Zhengzhou, China.

ABSTRACT
There is considerable variability between individuals in susceptibility to infection by human immunodeficiency virus (HIV). Many social, clinical and genetic factors are known to contribute to the likelihood of HIV transmission, but there is little consensus on the relative importance and potential interaction of these factors. Additionally, recent studies of several variants in chemokine receptors have identified alleles that may be predictive of HIV transmission and disease progression; however the strengths and directions of the associations of these genetic markers with HIV transmission have markedly varied between studies. To better identify factors that predict HIV transmission in a Chinese population, 180 cohabiting serodiscordant couples were enrolled for study by the Henan Center for Disease Prevention and Control, and transmission and progression of HIV infection were regularly measured. We found that anti-retroviral therapy, education level, and condom use were the most significant factors in determining likelihood of HIV transmission in this study. We also assessed ten variants in three genes (CXCL12, CCR2, and CCR5) that have been shown to influence HIV transmission. We found two tightly linked variants in CCR2 and CCR5, rs1799864 and rs1800024, have a significant positive association with transmission as recessive models (OR>10, P value=0.011). Mixed effects models showed that these genetic variants both retained significance when assessed with either treatment or condom use. These markers of transmission susceptibility may therefore serve to help stratify individuals by risk for HIV transmission.

No MeSH data available.


Related in: MedlinePlus

Linkage disequilibrium analysis of the CCR2 and CCR5 alleles included in this study.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4465854&req=5

pone.0129979.g002: Linkage disequilibrium analysis of the CCR2 and CCR5 alleles included in this study.

Mentions: All genotypes were assessed as recessive, dominant, and additive models. S1 Fig shows the variants studied and their relative positions in the genes CCR2, CCR5 and CXCL12. The CCR5 variants rs2856758 and rs333 did not occur as homozygous mutant in any individual in this study, and CCR5 rs41469351 was only present as homozygous wild type (Table 3). LD analysis shows that several of the CCR2-CCR5 alleles are tightly linked (Fig 2). The CCR2 variant rs1799864 and CCR5 rs1800024 showed a significant positive association (OR>10, P = 0.011) with transmission as recessive models (Table 4). No other model for other variants showed significance with transmission. Analysis was performed separately in the treated and untreated patients, however no untreated individuals who were homozygous mutant at rs1799864 and rs1800024 were found in this study. This subset analysis did not identify any additional alleles with significant association with transmission. Ten CCR2-CCR5 haplotypes were identified in this population, all haplotypes were assessed for association with other clinical variables when their frequency in the cohort was greater than 5%, and none showed a significant association with transmission (Table 5). Haplotypes are presented as alleles in the order: rs1799864, rs2856758, rs2734648, rs1799987, rs1799988, rs41469351, rs1800023, rs1800024, rs333 (the rs333 CCR5 Δ32 genotype was coded as I (insertion)/D (deletion)), and by a previously proposed phylogenetic-based nomenclature [19].


Analysis of Social and Genetic Factors Influencing Heterosexual Transmission of HIV within Serodiscordant Couples in the Henan Cohort.

Zhu Q, Zhu P, Zhang Y, Li J, Ma X, Li N, Wang Q, Xue X, Luo L, Li Z, Ring HZ, Ring BZ, Su L - PLoS ONE (2015)

Linkage disequilibrium analysis of the CCR2 and CCR5 alleles included in this study.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4465854&req=5

pone.0129979.g002: Linkage disequilibrium analysis of the CCR2 and CCR5 alleles included in this study.
Mentions: All genotypes were assessed as recessive, dominant, and additive models. S1 Fig shows the variants studied and their relative positions in the genes CCR2, CCR5 and CXCL12. The CCR5 variants rs2856758 and rs333 did not occur as homozygous mutant in any individual in this study, and CCR5 rs41469351 was only present as homozygous wild type (Table 3). LD analysis shows that several of the CCR2-CCR5 alleles are tightly linked (Fig 2). The CCR2 variant rs1799864 and CCR5 rs1800024 showed a significant positive association (OR>10, P = 0.011) with transmission as recessive models (Table 4). No other model for other variants showed significance with transmission. Analysis was performed separately in the treated and untreated patients, however no untreated individuals who were homozygous mutant at rs1799864 and rs1800024 were found in this study. This subset analysis did not identify any additional alleles with significant association with transmission. Ten CCR2-CCR5 haplotypes were identified in this population, all haplotypes were assessed for association with other clinical variables when their frequency in the cohort was greater than 5%, and none showed a significant association with transmission (Table 5). Haplotypes are presented as alleles in the order: rs1799864, rs2856758, rs2734648, rs1799987, rs1799988, rs41469351, rs1800023, rs1800024, rs333 (the rs333 CCR5 Δ32 genotype was coded as I (insertion)/D (deletion)), and by a previously proposed phylogenetic-based nomenclature [19].

Bottom Line: There is considerable variability between individuals in susceptibility to infection by human immunodeficiency virus (HIV).We found that anti-retroviral therapy, education level, and condom use were the most significant factors in determining likelihood of HIV transmission in this study.Mixed effects models showed that these genetic variants both retained significance when assessed with either treatment or condom use.

View Article: PubMed Central - PubMed

Affiliation: Institute for AIDS/STD Prevention and Control, Henan Center for Disease Prevention and Control, Zhengzhou, China.

ABSTRACT
There is considerable variability between individuals in susceptibility to infection by human immunodeficiency virus (HIV). Many social, clinical and genetic factors are known to contribute to the likelihood of HIV transmission, but there is little consensus on the relative importance and potential interaction of these factors. Additionally, recent studies of several variants in chemokine receptors have identified alleles that may be predictive of HIV transmission and disease progression; however the strengths and directions of the associations of these genetic markers with HIV transmission have markedly varied between studies. To better identify factors that predict HIV transmission in a Chinese population, 180 cohabiting serodiscordant couples were enrolled for study by the Henan Center for Disease Prevention and Control, and transmission and progression of HIV infection were regularly measured. We found that anti-retroviral therapy, education level, and condom use were the most significant factors in determining likelihood of HIV transmission in this study. We also assessed ten variants in three genes (CXCL12, CCR2, and CCR5) that have been shown to influence HIV transmission. We found two tightly linked variants in CCR2 and CCR5, rs1799864 and rs1800024, have a significant positive association with transmission as recessive models (OR>10, P value=0.011). Mixed effects models showed that these genetic variants both retained significance when assessed with either treatment or condom use. These markers of transmission susceptibility may therefore serve to help stratify individuals by risk for HIV transmission.

No MeSH data available.


Related in: MedlinePlus