AIDS. 32(15):2227–2236, SEPTEMBER 24, 2018

DOI: 10.1097/QAD.0000000000001932

,  

PMID: 30005021

Issn Print: 0269-9370

Publication Date: September 24, 2018


Share this on facebook   Share this on Twitter   Share this on LinkedIn   Email this article  



Print

Associations of human gene EPB41L3 DNA methylation and cervical intraepithelial neoplasia in women living with HIV-1 in Africa

Helen Kelly;Admire Chikandiwa;Rhian Warman;Michel Segondy;Bernard Sawadogo;Natasa Vasiljevic;Marie-Noelle Didelot;Nicolas Meda;Helen Weiss;Sinead Delany-Moretlwe;Philippe Mayaud;Attila Lorincz;

+ Author Information


    loading  Checking for direct PDF access through Ovid

Abstract

Objectives:To evaluate associations of DNA methylation of the human tumour suppressor gene EPB41L3 with high-grade cervical intraepithelial neoplasia (CIN2+) and HIV-related factors among women living with HIV-1 (WLHIV) in Burkina Faso and South Africa.Design:Case–control study of WLHIV aged 25–50 with histology-determined CIN2+ (cases, N = 152) and ≤CIN1 (controls, N = 210).Methods:EPB41L3 methylation was measured by pyrosequencing of bisulphite converted DNA from exfoliated cervical specimens at baseline and 16 months later. Median methylation levels were compared across CIN grades using the Mann–Whitney test and Cuzick test for trend. EPB41L3 methylation levels were dichotomized into ‘high’ and ‘low’ using the 66.7 percentile point of the distribution in the controls. Associations of EPB41L3 methylation with HIV-related factors were estimated by logistic regression.Results:Among 94 WLHIV in Burkina Faso and 268 in South Africa, median methylation levels at baseline for EPB41L3 increased with increasing CIN grade in both countries (P-trend <0.001).‘High’ methylation was more frequent among women with a longer time since HIV diagnosis in Burkina Faso [>5 years vs. ≤5 years; adjusted odds ratio (aOR) = 4.15, 95% CI 1.09–15.83, adjusted for age, CD4+ count, high-risk HPV and CIN status], with low CD4+ count in both countries (CD4+ ≤200 vs. ≥350 cells/μl: aOR = 7.14, 95% CI 1.44–35.37 in Burkina Faso; aOR = 2.55, 95% CI 1.07–6.07 in South Africa), and with prolonged ART use in South Africa (ART >2 years vs. ART-naïve: aOR = 2.40, 95% CI: 1.23–4.69).Conclusion:Methylation of EPB41L3 DNA is elevated among WLHIV with CIN2+ and independently associated with lower CD4+ count and ART use.

Related Topics

    Related Articles

        loading  Loading Related Articles