甘露糖结合凝集素缺乏在津巴布韦农村成年人群中HIV-1和血吸虫感染中的作用
Role of mannose-binding lectin deficiency in HIV-1 and schistosoma infections in a rural adult population in Zimbabwe.
作者信息
Zinyama-Gutsire Rutendo B L, Chasela Charles, Madsen Hans O, Rusakaniko Simbarashe, Kallestrup Per, Christiansen Michael, Gomo Exnevia, Ullum Henrik, Erikstrup Christian, Munyati Shungu, Kurewa Edith N, Stray-Pedersen Babill, Garred Peter, Mduluza Takafira
机构信息
Faculty of Health Sciences, School of Public Health, University of the Witwatersrand, Johannesburg, South Africa; Medical Research Council of Zimbabwe, Ministry of Health and Child Welfare, Harare, Zimbabwe; Letten Research Foundation, Harare, Zimbabwe.
Faculty of Health Sciences, School of Public Health, University of the Witwatersrand, Johannesburg, South Africa.
出版信息
PLoS One. 2015 Apr 1;10(4):e0122659. doi: 10.1371/journal.pone.0122659. eCollection 2015.
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 54A>G), C (codon 57A>G), and D (codon 52T>C) 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 800μg/L (192-1936μg/L). Prevalence of plasma MBL deficiency was 18% with high frequency of the C (codon 57G>A) mutant allele (20%). There was no significant difference in median plasma MBL levels between HIV negative (912μg/L) and HIV positive (688μg/L), p = 0.066. However plasma MBL levels at the assay detection limit of 20μg/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.
背景
MBL2基因多态性导致MBL缺乏，已表明这会增加对各种细菌、病毒和寄生虫感染的易感性。我们评估了MBL缺乏在参与穆普富雷血吸虫病和艾滋病毒队列（MUSH队列）的津巴布韦成年人中对HIV-1和血吸虫感染的作用。
方法
在基线时确定HIV-1、埃及血吸虫和曼氏血吸虫感染情况。通过ELISA测定血浆MBL浓度，通过PCR确定MBL2基因型。我们使用卡方检验计算并比较了HIV-1和血吸虫合并感染组与对照组之间血浆MBL缺乏、MBL2结构变异等位基因B（密码子54A>G）、C（密码子57A>G）和D（密码子52T>C）以及MBL2启动子变异-550（H/L）、-221（X/Y）和+4（P/Q）的比例。
结果
我们评估了379名成年人，其中80%为女性，中位年龄（四分位间距）为30（17-41）岁。在MUSH基线调查中，HIV-1、埃及血吸虫和曼氏血吸虫的患病率分别为26%、43%和18%。血浆MBL浓度中位数（四分位间距）为800μg/L（192-1936μg/L）。血浆MBL缺乏的患病率为18%，C（密码子57G>A）突变等位基因频率较高（20%）。HIV阴性者（912μg/L）和HIV阳性者（688μg/L）的血浆MBL水平中位数无显著差异，p = 0.066。然而，在HIV-1感染者中，血浆MBL水平在检测下限20μg/L时更为常见（p = 0.007）。感染埃及血吸虫和曼氏血吸虫的参与者的MBL水平显著高于未感染者。所有MBL2变异均与HIV-1感染无关，但启动子变异LY和LL与埃及血吸虫感染显著相关。
结论
我们的数据表明MBL缺乏的患病率很高，没有证据表明MBL缺乏与HIV-1感染之间存在关联。然而，较低的血浆MBL水平对埃及血吸虫和曼氏血吸虫感染均有保护作用，MBL2启动子及变异LY和LL增加了对埃及血吸虫感染的易感性。
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