Regional variation in CCR5-Δ32 gene distribution among women from the US HIV Epidemiology Research Study (HERS)

Downer, Marie; Hodge, Thomas; Smith, Dawn K.; Qari, Shoukat H.; Schuman, Paula; Mayer, Kenneth H.; Klein, Robert S.; Vlahov, David; Gardner, Lytt I.; McNicholl, Janet M.

doi:10.1038/sj.gene.6363884

Genes Immun

2002

DOI: 10.1038/sj.gene.6363884

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Regional variation in CCR5-Δ32 gene distribution among women from the US HIV Epidemiology Research Study (HERS)

Marie Downer

Thomas Hodge

Dawn K. Smith

et al.

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Cited by 11 publications

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“…CCR5-D32 homozygote frequency was also higher in our deceased patient group (9.1 %; 1 of 11) than in the general population (,1 %) (Downer et al, 2002;Rodríguez-Rodríguez et al, 2011), although the small sample size might not be representative. We thus found a higher prevalence of the CCR5-D32 allele in homo-or heterozygosis patients (36.4 %; 4 of 11; Table 2) compared with that in the general population (11-16 %) (Downer et al, 2002;Rodríguez-Rodríguez et al, 2011). These results establish a clear correlation between the CCR5 genotype and the fatality rate of A(H1N1)2009-infected patients.…”

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confidence: 86%

“…This proportion increased to 33.3 % for CCR5-D32 homozygous patients, although the small sample size did not provide adequate statistical power. The frequency of CCR5-D32 heterozygous individuals was consistently higher (27.3 %; 3 of 11; Table 2) in the deceased patient cohort than it was in the general population (10-15 %) (Downer et al, 2002;Rodríguez-Rodríguez et al, 2011). CCR5-D32 homozygote frequency was also higher in our deceased patient group (9.1 %; 1 of 11) than in the general population (,1 %) (Downer et al, 2002;Rodríguez-Rodríguez et al, 2011), although the small sample size might not be representative.…”

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confidence: 99%

“…The frequency of CCR5-D32 heterozygous individuals was consistently higher (27.3 %; 3 of 11; Table 2) in the deceased patient cohort than it was in the general population (10-15 %) (Downer et al, 2002;Rodríguez-Rodríguez et al, 2011). CCR5-D32 homozygote frequency was also higher in our deceased patient group (9.1 %; 1 of 11) than in the general population (,1 %) (Downer et al, 2002;Rodríguez-Rodríguez et al, 2011), although the small sample size might not be representative. We thus found a higher prevalence of the CCR5-D32 allele in homo-or heterozygosis patients (36.4 %; 4 of 11; Table 2) compared with that in the general population (11-16 %) (Downer et al, 2002;Rodríguez-Rodríguez et al, 2011).…”

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confidence: 99%

“…global distribution of CCR5-D32 heterozygous individuals depends on race/ethnic group, with mean values ranging from 9.9 to 15 %; it is more frequent in Caucasians, irregular in native Amerindians, and rare or absent in other major ethnic groups such as native Africans and Asians (Libert et al, 1998; Rodríguez-Rodríguez et al, 2011;Zimmerman et al, 1997). Detection of CCR5-D32 homozygous individuals is rare, with a mean value of ,1 % (Downer et al, 2002; Rodríguez-Rodríguez et al, 2011).The CCR5-D32 allele reduces susceptibility to human immunodeficiency virus infection (Dean et al, 1996;Liu et al, 1996;Samson et al, 1996). Homozygosity for the CCR5-D32 allele is a strong risk factor for symptomatic West Nile virus infection (Lim et al, 2008) and correlates with disease severity after tick-borne encephalitis virus infection (Kindberg et al, 2008).…”

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confidence: 99%

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confidence: 99%

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CCR5 deficiency predisposes to fatal outcome in influenza virus infection

Falcón

Cuevas

Rodríguez-Frandsen

et al. 2015

Journal of General Virology

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Influenza epidemics affect all age groups, although children, the elderly and those with underlying medical conditions are the most severely affected. Whereas co-morbidities are present in 50 % of fatal cases, 25-50 % of deaths are in apparently healthy individuals. This suggests underlying genetic determinants that govern infection severity. Although some viral factors that contribute to influenza disease are known, the role of host genetic factors remains undetermined. Data for small cohorts of influenza-infected patients are contradictory regarding the potential role of chemokine receptor 5 deficiency (CCR5-D32 mutation, a 32 bp deletion in the CCR5 gene) in the outcome of influenza virus infection. We tested 171 respiratory samples from influenza patients (2009 pandemic) for CCR5-D32 and evaluated its correlation with patient mortality. CCR5-D32 patients (17.4 %) showed a higher mortality rate than WT individuals (4.7 %; P50.021), which indicates that CCR5-D32 patients are at higher risk than the normal population of a fatal outcome in influenza infection. Influenza A viruses are a major source of acute respiratory infections and continue to be an important cause of acute illness and death worldwide. They cause annual epidemics and occasional pandemics with potentially fatal outcome. The mean global burden of seasonal influenza is more than 600 million cases, with 3 million cases of severe illness and almost 500 000 deaths per year worldwide (http://www. who.int/en/). A new H1N1 subtype influenza A virus emerged in 2009 [A(H1N1)pdm09], which was highly transmissible with relatively low virulence and caused the first pandemic of the 21st century (Neumann et al., 2009).Differences in disease severity can be due to pre-existing health conditions, predisposing host genetic factors, differences in the virulence of circulating viruses or a combination of these factors. The co-morbid conditions for A(H1N1)pdm09 include chronic metabolic disease, primarily diabetes mellitus and renal disease, chronic lung and cardiac disease, immunosuppressive conditions, neoplasms, obesity and pregnancy (Falagas et al., 2011; Louie et al., 2011;Singanayagam et al., 2011).Although co-morbidities are present in half of fatal cases, one-third of fatal cases have no co-morbid conditions (http://www.cdc.gov/h1n1flu/estimates_2009_h1n1.htm), suggesting that host genetic variation accounts for the distinct disease severity of A(H1N1)pdm09 infection. Several potential genetic determinants associated with A(H1N1)pdm09 infection have been described, including TNF (Antonopoulou et al., 2012), IFN-inducible transmembrane (Everitt et al., 2012), killer-cell immunoglobulin-like receptor (Aranda-Romo et al., 2012), complement regulatory protein CD55 (Zhou et al., 2012) and Toll-like receptor 3 (Esposito et al., 2012). Data relating to the role of chemokine receptor 5 (CCR5) in severe A(H1N1)pdm09-infected patients are contradictory and have been debated (Keynan et al., 2010;Rodriguez et al., 2013;Sironi et al., 2014).CCR5 regulates various aspec...

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confidence: 86%

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confidence: 99%

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confidence: 99%

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confidence: 99%

mentioning

confidence: 99%

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CCR5 deficiency predisposes to fatal outcome in influenza virus infection

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Rodríguez-Frandsen

et al. 2015

Journal of General Virology

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Impact of CCR2 and SDF1 Polymorphisms on Disease Progression in HIV‐Infected Subjects in Thailand

Ammaranond¹,

Sanguansitthianan

Phaengchomduan

et al. 2013

Clinical Laboratory Analysis

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Association of chemokines receptor (CCR5 Δ32) in idiopathic recurrent miscarriages among north Indians

Parveen

Tripathi

Singh

et al. 2008

Arch Gynecol Obstet

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Regional variation in CCR5-Δ32 gene distribution among women from the US HIV Epidemiology Research Study (HERS)

Cited by 11 publications

References 14 publications

CCR5 deficiency predisposes to fatal outcome in influenza virus infection

CCR5 deficiency predisposes to fatal outcome in influenza virus infection

Impact of CCR2 and SDF1 Polymorphisms on Disease Progression in HIV‐Infected Subjects in Thailand

Association of chemokines receptor (CCR5 Δ32) in idiopathic recurrent miscarriages among north Indians

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