Role of mannose-binding lectin deficiency in HIV-1 and schistosoma infections in a rural adult population in Zimbabwe

Rutendo B L Zinyama-Gutsire; Charles Chasela; Hans O. Madsen; Simbarashe Rusakaniko; Per Kallestrup; Michael Christiansen; Exnevia Gomo; Henrik Ullum; Christian Erikstrup; Shungu Munyati; Edith N Kurewa; Babill Stray-Pedersen; Peter Garred; Takafira Mduluza

doi:10.1371/journal.pone.0122659

Role of mannose-binding lectin deficiency in HIV-1 and schistosoma infections in a rural adult population in Zimbabwe

Rutendo B L Zinyama-Gutsire, Charles Chasela, Hans O. Madsen, Simbarashe Rusakaniko, Per Kallestrup, Michael Christiansen, Exnevia Gomo, Henrik Ullum, Christian Erikstrup, Shungu Munyati, Edith N Kurewa, Babill Stray-Pedersen, Peter Garred, Takafira Mduluza

Institut for Klinisk Medicin

9 Citationer (Scopus)

Abstract

Background Polymorphism in the MBL2 gene lead to MBL deficiency, which has been shown to increase susceptibility to various bacterial, viral and parasitic infections. We assessed role of MBL deficiency in HIV-1 and schistosoma infections in Zimbabwean adults enrolled in the Mupfure Schistosomiasis and HIV Cohort (MUSH Cohort). Methods HIV-1, S. haematobium and S. mansoni infections were determined at baseline. Plasma MBL concentration was measured by ELISA and MBL2 genotypes determined by PCR.We calculated and compared the proportions of plasma MBL deficiency, MBL2 structural variant alleles B (codon 54AG), C (codon 57AG), and D (codon 52TC) as well as MBL2 promoter variants -550(H/L), -221(X/Y) and +4(P/Q) between HIV-1 and schistosoma co-infection and control groups using Chi Square test. Results We assessed 379 adults, 80% females, median age (IQR) 30 (17-41) years. HIV-1, S. haematobium and S. mansoni prevalence were 26%, 43% and 18% respectively in the MUSH baseline survey. Median (IQR) plasma MBL concentration was 800g/L (192-1936 g/L). Prevalence of plasma MBL deficiency was 18% with high frequency of the C (codon 57GA) mutant allele (20%). There was no significant difference in median plasma MBL levels between HIV negative (912g/L) and HIV positive (688g/L), p = 0.066. However plasma MBL levels at the assay detection limit of 20g/L were more frequent among the HIV-1 infected (p = 0.007). S. haematobium and S. mansoni infected participants had significantly higher MBL levels than uninfected. All MBL2 variants were not associated with HIV-1 infection but promoter variants LY and LL were significantly associated with S. haematobium infection. Conclusion Our data indicate high prevalence of MBL deficiency, no evidence of association between MBL deficiency and HIV-1 infection. However, lower plasma MBL levels were protective against both S. haematobium and S. mansoni infections and MBL2 promoter and variants LY and LL increased susceptibility to S . haematobium infection.

Originalsprog	Engelsk
Artikelnummer	e0122659
Tidsskrift	P L o S One
Vol/bind	10
Udgave nummer	4
Sider (fra-til)	1-23
Antal sider	23
ISSN	1932-6203
DOI	https://doi.org/10.1371/journal.pone.0122659
Status	Udgivet - 1 apr. 2015

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10.1371/journal.pone.0122659

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Zinyama-Gutsire, R. B. L., Chasela, C., Madsen, H. O., Rusakaniko, S., Kallestrup, P., Christiansen, M., Gomo, E., Ullum, H., Erikstrup, C., Munyati, S., Kurewa, E. N., Stray-Pedersen, B., Garred, P., & Mduluza, T. (2015). Role of mannose-binding lectin deficiency in HIV-1 and schistosoma infections in a rural adult population in Zimbabwe. P L o S One, 10(4), 1-23. [e0122659]. https://doi.org/10.1371/journal.pone.0122659

Zinyama-Gutsire, RBL, Chasela, C, Madsen, HO, Rusakaniko, S, Kallestrup, P, Christiansen, M, Gomo, E, Ullum, H, Erikstrup, C, Munyati, S, Kurewa, EN, Stray-Pedersen, B, Garred, P & Mduluza, T 2015, 'Role of mannose-binding lectin deficiency in HIV-1 and schistosoma infections in a rural adult population in Zimbabwe', P L o S One, bind 10, nr. 4, e0122659, s. 1-23. https://doi.org/10.1371/journal.pone.0122659

@article{fbd79a091f474c7e926fac5f4c89392c,

title = "Role of mannose-binding lectin deficiency in HIV-1 and schistosoma infections in a rural adult population in Zimbabwe",

abstract = "Background Polymorphism in the MBL2 gene lead to MBL deficiency, which has been shown to increase susceptibility to various bacterial, viral and parasitic infections. We assessed role of MBL deficiency in HIV-1 and schistosoma infections in Zimbabwean adults enrolled in the Mupfure Schistosomiasis and HIV Cohort (MUSH Cohort). Methods HIV-1, S. haematobium and S. mansoni infections were determined at baseline. Plasma MBL concentration was measured by ELISA and MBL2 genotypes determined by PCR.We calculated and compared the proportions of plasma MBL deficiency, MBL2 structural variant alleles B (codon 54AG), C (codon 57AG), and D (codon 52TC) as well as MBL2 promoter variants -550(H/L), -221(X/Y) and +4(P/Q) between HIV-1 and schistosoma co-infection and control groups using Chi Square test. Results We assessed 379 adults, 80% females, median age (IQR) 30 (17-41) years. HIV-1, S. haematobium and S. mansoni prevalence were 26%, 43% and 18% respectively in the MUSH baseline survey. Median (IQR) plasma MBL concentration was 800g/L (192-1936 g/L). Prevalence of plasma MBL deficiency was 18% with high frequency of the C (codon 57GA) mutant allele (20%). There was no significant difference in median plasma MBL levels between HIV negative (912g/L) and HIV positive (688g/L), p = 0.066. However plasma MBL levels at the assay detection limit of 20g/L were more frequent among the HIV-1 infected (p = 0.007). S. haematobium and S. mansoni infected participants had significantly higher MBL levels than uninfected. All MBL2 variants were not associated with HIV-1 infection but promoter variants LY and LL were significantly associated with S. haematobium infection. Conclusion Our data indicate high prevalence of MBL deficiency, no evidence of association between MBL deficiency and HIV-1 infection. However, lower plasma MBL levels were protective against both S. haematobium and S. mansoni infections and MBL2 promoter and variants LY and LL increased susceptibility to S . haematobium infection.",

keywords = "Adolescent, Adult, Coinfection, Female, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, HIV Infections, HIV-1, Humans, Male, Mannose-Binding Lectin, Metabolism, Inborn Errors, Polymorphism, Single Nucleotide, Prevalence, Promoter Regions, Genetic, Rural Population, Schistosomiasis haematobia, Schistosomiasis mansoni, Young Adult, Zimbabwe",

author = "Zinyama-Gutsire, {Rutendo B L} and Charles Chasela and Madsen, {Hans O.} and Simbarashe Rusakaniko and Per Kallestrup and Michael Christiansen and Exnevia Gomo and Henrik Ullum and Christian Erikstrup and Shungu Munyati and Kurewa, {Edith N} and Babill Stray-Pedersen and Peter Garred and Takafira Mduluza",

year = "2015",

month = apr,

day = "1",

doi = "10.1371/journal.pone.0122659",

language = "English",

volume = "10",

pages = "1--23",

journal = "PLoS Computational Biology",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "4",

}

TY - JOUR

T1 - Role of mannose-binding lectin deficiency in HIV-1 and schistosoma infections in a rural adult population in Zimbabwe

AU - Zinyama-Gutsire, Rutendo B L

AU - Chasela, Charles

AU - Madsen, Hans O.

AU - Rusakaniko, Simbarashe

AU - Kallestrup, Per

AU - Christiansen, Michael

AU - Gomo, Exnevia

AU - Ullum, Henrik

AU - Erikstrup, Christian

AU - Munyati, Shungu

AU - Kurewa, Edith N

AU - Stray-Pedersen, Babill

AU - Garred, Peter

AU - Mduluza, Takafira

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Background Polymorphism in the MBL2 gene lead to MBL deficiency, which has been shown to increase susceptibility to various bacterial, viral and parasitic infections. We assessed role of MBL deficiency in HIV-1 and schistosoma infections in Zimbabwean adults enrolled in the Mupfure Schistosomiasis and HIV Cohort (MUSH Cohort). Methods HIV-1, S. haematobium and S. mansoni infections were determined at baseline. Plasma MBL concentration was measured by ELISA and MBL2 genotypes determined by PCR.We calculated and compared the proportions of plasma MBL deficiency, MBL2 structural variant alleles B (codon 54AG), C (codon 57AG), and D (codon 52TC) as well as MBL2 promoter variants -550(H/L), -221(X/Y) and +4(P/Q) between HIV-1 and schistosoma co-infection and control groups using Chi Square test. Results We assessed 379 adults, 80% females, median age (IQR) 30 (17-41) years. HIV-1, S. haematobium and S. mansoni prevalence were 26%, 43% and 18% respectively in the MUSH baseline survey. Median (IQR) plasma MBL concentration was 800g/L (192-1936 g/L). Prevalence of plasma MBL deficiency was 18% with high frequency of the C (codon 57GA) mutant allele (20%). There was no significant difference in median plasma MBL levels between HIV negative (912g/L) and HIV positive (688g/L), p = 0.066. However plasma MBL levels at the assay detection limit of 20g/L were more frequent among the HIV-1 infected (p = 0.007). S. haematobium and S. mansoni infected participants had significantly higher MBL levels than uninfected. All MBL2 variants were not associated with HIV-1 infection but promoter variants LY and LL were significantly associated with S. haematobium infection. Conclusion Our data indicate high prevalence of MBL deficiency, no evidence of association between MBL deficiency and HIV-1 infection. However, lower plasma MBL levels were protective against both S. haematobium and S. mansoni infections and MBL2 promoter and variants LY and LL increased susceptibility to S . haematobium infection.

AB - Background Polymorphism in the MBL2 gene lead to MBL deficiency, which has been shown to increase susceptibility to various bacterial, viral and parasitic infections. We assessed role of MBL deficiency in HIV-1 and schistosoma infections in Zimbabwean adults enrolled in the Mupfure Schistosomiasis and HIV Cohort (MUSH Cohort). Methods HIV-1, S. haematobium and S. mansoni infections were determined at baseline. Plasma MBL concentration was measured by ELISA and MBL2 genotypes determined by PCR.We calculated and compared the proportions of plasma MBL deficiency, MBL2 structural variant alleles B (codon 54AG), C (codon 57AG), and D (codon 52TC) as well as MBL2 promoter variants -550(H/L), -221(X/Y) and +4(P/Q) between HIV-1 and schistosoma co-infection and control groups using Chi Square test. Results We assessed 379 adults, 80% females, median age (IQR) 30 (17-41) years. HIV-1, S. haematobium and S. mansoni prevalence were 26%, 43% and 18% respectively in the MUSH baseline survey. Median (IQR) plasma MBL concentration was 800g/L (192-1936 g/L). Prevalence of plasma MBL deficiency was 18% with high frequency of the C (codon 57GA) mutant allele (20%). There was no significant difference in median plasma MBL levels between HIV negative (912g/L) and HIV positive (688g/L), p = 0.066. However plasma MBL levels at the assay detection limit of 20g/L were more frequent among the HIV-1 infected (p = 0.007). S. haematobium and S. mansoni infected participants had significantly higher MBL levels than uninfected. All MBL2 variants were not associated with HIV-1 infection but promoter variants LY and LL were significantly associated with S. haematobium infection. Conclusion Our data indicate high prevalence of MBL deficiency, no evidence of association between MBL deficiency and HIV-1 infection. However, lower plasma MBL levels were protective against both S. haematobium and S. mansoni infections and MBL2 promoter and variants LY and LL increased susceptibility to S . haematobium infection.

KW - Adolescent

KW - Adult

KW - Coinfection

KW - Female

KW - Gene Frequency

KW - Genetic Association Studies

KW - Genetic Predisposition to Disease

KW - HIV Infections

KW - HIV-1

KW - Humans

KW - Male

KW - Mannose-Binding Lectin

KW - Metabolism, Inborn Errors

KW - Polymorphism, Single Nucleotide

KW - Prevalence

KW - Promoter Regions, Genetic

KW - Rural Population

KW - Schistosomiasis haematobia

KW - Schistosomiasis mansoni

KW - Young Adult

KW - Zimbabwe

U2 - 10.1371/journal.pone.0122659

DO - 10.1371/journal.pone.0122659

M3 - Journal article

C2 - 25830474

SN - 1932-6203

VL - 10

SP - 1

EP - 23

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 4

M1 - e0122659

ER -

Role of mannose-binding lectin deficiency in HIV-1 and schistosoma infections in a rural adult population in Zimbabwe

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