Torres-Rojas Andrea, González-Hernández Luz Alicia, Sánchez-Reyes Karina, Chávez-Iñiguez Jonathan Samuel, Topete-Reyes Jorge Fernando, Andrade-Villanueva Jaime Federico, Martínez-Ayala Pedro, Valle-Rodriguez Adriana, Ruiz-Herrera Vida Verónica, Hernández-Bello Jorge, Reyes-Castillo Zyanya, Álvarez-Zavala Monserrat
Molecular Biology in Medicine, CUCS- University of Guadalajara, Guadalajara, México.
HIV Unit, Antiguo Hospital Civil of Guadalajara "Fray Antonio Alcalde", Guadalajara, México.
BMC Nephrol. 2025 May 14;26(1):236. doi: 10.1186/s12882-025-04138-8.
The CKD in PLHIV is highly prevalent in Jalisco. Despite its control with ART, HIV is characterized by generating low-grade inflammation events that contribute to the development and progression of CKD. Considering the importance of hs-CRP in the context of CKD, various genetic predisposition studies have been conducted to search for variants of the CRP gene, among which the SNV rs2808630 has been associated with serum hs-CRP concentrations and progression of CKD. Due to the above, there is interest in studying this SNV, addressing the limited information available on this topic in Mexico.
The case-control study included 163 patients with CKD, 102 PLHIV with CKD under ART with undetectable viral loads from the Hospital Civil of Guadalajara "Fray Antonio Alcalde" and 115 controls. Clinical assessment and general laboratory studies were carried out. Also, serum quantification of inflammatory biomarkers was performed by ELISA method. The determination of CRP SNV rs2808630 by qPCR and the association with inflammatory biomarkers was evaluated. Statistical analysis was carried out considering significant values p < 0.05.
Lower prevalence of CC genotype was shown in our population. Of the 358 samples, 221 (61.7%) present the wild-type genotype. The results analyzed correspond with what has been reported worldwide in studies of CRP SNV rs2808630 in the development of CKD without having a relationship with inflammatory and kidney function biomarkers. However, higher creatinine and IL-6 concentrations were observed in the group with the CC genotype. A significant correlation between IL-6 and eGFR was identified in CKD patients, but not for PLHIV with CKD, highlighting a potential difference in inflammatory dynamics between these groups. Importantly, in PLHIV with CKD, we found a strong correlation between hs-CRP and IL-8, suggesting a possible association with a higher proportion of the inflammatory isoform of hs-CRP, which may have implications for disease progression and cardiovascular risk.
The presence of the CRP SNV does not appear to contribute to the development of CKD and has no association with inflammatory biomarkers. Though, genetically independent manner, hs-CRP levels are slightly different between groups and are underrated when related to the CKD stage in PLHIV. Also, high IL-6 concentrations are related to CKD progression, while IL-8 seems to have a better relation to CKD in PLHIV.
在哈利斯科州，感染艾滋病毒的慢性肾脏病患者极为普遍。尽管通过抗逆转录病毒疗法（ART）进行了控制，但艾滋病毒的特点是会引发低度炎症反应，这会促使慢性肾脏病的发生和发展。鉴于高敏C反应蛋白（hs-CRP）在慢性肾脏病背景下的重要性，已经开展了各种基因易感性研究来寻找C反应蛋白（CRP）基因的变体，其中单核苷酸变异（SNV）rs2808630与血清hs-CRP浓度及慢性肾脏病的进展有关。基于上述情况，人们有兴趣研究这种SNV，以解决墨西哥关于该主题的可用信息有限的问题。
病例对照研究纳入了163例慢性肾脏病患者、102例来自瓜达拉哈拉“弗雷·安东尼奥·阿尔calde”市民医院且接受ART治疗且病毒载量不可检测的感染艾滋病毒的慢性肾脏病患者以及115名对照者。进行了临床评估和常规实验室检查。此外，通过酶联免疫吸附测定（ELISA）法对炎症生物标志物进行血清定量分析。通过定量聚合酶链反应（qPCR）测定CRP SNV rs2808630，并评估其与炎症生物标志物的关联。考虑p < 0.05的显著值进行统计分析。
我们的人群中CC基因型的患病率较低。在358个样本中，221个（61.7%）呈现野生型基因型。分析结果与全球范围内关于CRP SNV rs2808630在慢性肾脏病发展中的研究报告一致，且与炎症和肾功能生物标志物无关。然而，在CC基因型组中观察到肌酐和白细胞介素-6（IL-6）浓度较高。在慢性肾脏病患者中发现IL-6与估算肾小球滤过率（eGFR）之间存在显著相关性，但感染艾滋病毒的慢性肾脏病患者中未发现，这突出了这些组之间炎症动态的潜在差异。重要的是，在感染艾滋病毒的慢性肾脏病患者中，我们发现hs-CRP与IL-8之间存在强相关性，这表明可能与hs-CRP炎症异构体的比例较高有关，这可能对疾病进展和心血管风险产生影响。
CRP SNV的存在似乎对慢性肾脏病的发展没有影响，且与炎症生物标志物无关。不过，在基因独立的情况下，各组之间hs-CRP水平略有不同，并且在与感染艾滋病毒的慢性肾脏病患者的慢性肾脏病阶段相关时被低估。此外，高IL-6浓度与慢性肾脏病进展相关，而IL-8似乎与感染艾滋病毒的慢性肾脏病患者的慢性肾脏病关系更好。
