Department of Medicine Aminu Kano Teaching Hospital/ Bayero University Kano, Kano, Nigeria.
Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
PLoS One. 2022 Oct 13;17(10):e0275949. doi: 10.1371/journal.pone.0275949. eCollection 2022.
Racial disparities are known in the occurrence of kidney disease with excess risks found among people of African descent. Apolipoprotein L1 (APOL1) gene variants G1 and G2 are associated with kidney disease among HIV infected individuals of African descent in the USA as well as among black population in South Africa. We set out to investigate the prevalence of these high-risk variants and their effects on kidney disease among HIV infected patients in Northern Nigeria with hitherto limited information despite earlier reports of high population frequencies of these alleles from the Southern part of the country.
DNA samples obtained from the whole blood of 142 participants were genotyped for APOL1 G1 and G2 variants after initial baseline investigations including assessment of kidney function. Participants comprised 50 HIV positive patients with no evidence of kidney disease, 52 HIV negative individuals with no kidney disease and 40 HIV positive patients with chronic kidney disease (CKD) evidenced by persistent proteinuria and/or reduced eGFR, who also had a kidney biopsy. All the HIV positive patients were newly diagnosed and treatment naïve.
The distribution of the APOL1 genotypes among the study participants revealed that 24.6% had a G1 risk allele and 19.0% a G2. The frequency of the High Risk Genotype (HRG) was 12.5% among those with CKD compared to 5.8% in the HIV negative group and zero in the HIV positive no CKD group. Having the HRG was associated with a higher odds for developing HIV Associated Nephropathy (HIVAN) (2 vs 0 risk alleles: OR 10.83, 95% CI 1.38-84.52; P = 0.023; 2 vs 0 or 1 risk alleles: OR 5.5, 95% CI 0.83-36.29; P = 0.07). The HRG was also associated with higher odds for Focal Segmental Glomerulosclerosis (FSGS) (2 vs 0 risk alleles: OR 13.0, 95% CI 2.06-81.91; P = 0.006 and 2 vs 0 or 1 risk alleles: OR 9.0, 95%CI 1.62-50.12; P = 0.01) when compared to the control group.
This study showed a high population frequency of the individual risk alleles of the APOL1 gene with higher frequencies noted among HIV positive patients with kidney disease. There is high association with the presence of kidney disease and especially FSGS and HIVAN among treatment naive HIV patients carrying two copies of the HRG.
在肾脏病的发生中存在种族差异，非洲裔人群的患病风险更高。载脂蛋白 L1（APOL1）基因变体 G1 和 G2 与美国非洲裔感染 HIV 人群以及南非黑人人群中的肾脏病有关。我们着手调查这些高危变体在尼日利亚北部 HIV 感染患者中的流行情况，尽管该国南部早些时候报告了这些等位基因的高人群频率，但迄今为止，有关该地区的信息仍然有限。
对 142 名参与者的全血 DNA 样本进行 APOL1 G1 和 G2 变体的基因分型，这些参与者在初步基线调查后进行了基因分型，包括肾功能评估。参与者包括 50 名无肾脏疾病证据的 HIV 阳性患者、52 名无肾脏疾病的 HIV 阴性个体和 40 名慢性肾脏病（CKD）的 HIV 阳性患者，这些患者通过持续蛋白尿和/或降低的 eGFR 证实存在 CKD，且这些患者均进行了肾脏活检。所有 HIV 阳性患者均为初诊且未接受治疗。
研究参与者的 APOL1 基因型分布显示，24.6%的人携带 G1 风险等位基因，19.0%的人携带 G2 风险等位基因。与 HIV 阴性组的 5.8%和 HIV 阳性无 CKD 组的 0%相比，CKD 患者的高危基因型（HRG）频率为 12.5%。携带 HRG 与发生 HIV 相关性肾病（HIVAN）的几率更高（2 个风险等位基因与 0 个风险等位基因：OR 10.83，95%CI 1.38-84.52；P = 0.023；2 个风险等位基因与 0 个或 1 个风险等位基因：OR 5.5，95%CI 0.83-36.29；P = 0.07）。HRG 还与局灶节段性肾小球硬化（FSGS）的几率更高相关（2 个风险等位基因与 0 个风险等位基因：OR 13.0，95%CI 2.06-81.91；P = 0.006；2 个风险等位基因与 0 个或 1 个风险等位基因：OR 9.0，95%CI 1.62-50.12；P = 0.01），与对照组相比。
本研究显示 APOL1 基因个体风险等位基因的人群频率较高，在有肾脏病的 HIV 阳性患者中频率更高。在携带两份 HRG 的治疗初治 HIV 患者中，HRG 与肾脏病的存在，特别是 FSGS 和 HIVAN 高度相关。
