Department of Molecular Biology, ICMR-National AIDS Research Institute, Pune, 411026, India.
Department of Molecular Biology, ICMR-National AIDS Research Institute, Pune, 411026, India.
Microb Pathog. 2021 Dec;161(Pt A):105243. doi: 10.1016/j.micpath.2021.105243. Epub 2021 Oct 14.
Kinase insert Domain containing Receptor (KDR)/Vascular Endothelial Growth Factor Receptor (VEGFR-2) participate in endothelial dysfunction, which can lead to chronic liver disease. KDR reflects naturally against the toxicants from the damaged liver cells. Association of KDR polymorphism has been reported with many diseases including liver disease, but its role has not been described in ARV induced hepatotoxicity. Hence, we examined the exonic regions KDR (1192G/A, 1719A/T) polymorphism from 165 HIV-infected individuals (34/165 had ARV induced hepatotoxicity, 131/165 were with no hepatotoxicity) and 160 normal uninfected individuals by PCR-RFLP. In univariate analysis, KDR 1719 TT genotype presented at greater frequency from all HIV positive individuals in contrast with normal uninfected individuals (7.87% vs. 4.4%, OR = 1.72, P = 0.38). Individuals with KDR 1719 TT genotype had a risk for increasing hepatotoxicity and its severity (OR = 1.91, P = 0.38). Individuals with haplotype AT had risk for increasing hepatotoxicity and its severity (OR = 1.60, P = 0.50; OR = 2.35, P = 0.27). Whereas haplotype AA was associated with reduced risk of developing hepatotoxicity (OR = 0.40, P = 0.04). Individuals with KDR 1719 TT genotype were at greater risk of advancement of HIV disease (OR = 2.31, P = 0.23). Individuals with KDR 1719 TT genotype had more vulnerability for developing hepatotoxicity among alcohol users (OR = 2.57, P = 0.23). Individuals with KDR 1719 TT genotype were at higher risk of developing hepatotoxicity and its severity among nevirapine and alcohol consumers (OR = 2.47, P = 0.24; OR = 5.42, P = 0.42). In multivariate analysis, hepatotoxicity patients taking ART inclusive of nevirapine was associated with the severity of hepatotoxicity (OR = 4.82, P = 0.002). In conclusion, KDR 1719 TT genotype and haplotype AT may have a risk for development of hepatotoxicity and its severity. Haplotype AA may have influence to reduce the risk of developing hepatotoxicity.
激酶插入结构域受体（KDR）/血管内皮生长因子受体（VEGFR-2）参与内皮功能障碍，可导致慢性肝病。KDR 自然抵抗来自受损肝细胞的毒物。已经报道 KDR 多态性与许多疾病有关，包括肝病，但在 ARV 诱导的肝毒性中其作用尚未描述。因此，我们通过 PCR-RFLP 检查了 165 名 HIV 感染个体（34/165 名发生 ARV 诱导的肝毒性，131/165 名无肝毒性）和 160 名正常未感染个体的 KDR（1192G/A、1719A/T）外显子区多态性。在单变量分析中，与正常未感染个体相比，所有 HIV 阳性个体中 KDR 1719 TT 基因型的频率更高（7.87%对 4.4%，OR=1.72，P=0.38）。KDR 1719 TT 基因型个体发生肝毒性及其严重程度的风险增加（OR=1.91，P=0.38）。AT 单倍型个体发生肝毒性及其严重程度的风险增加（OR=1.60，P=0.50；OR=2.35，P=0.27）。而 AA 单倍型与发生肝毒性的风险降低相关（OR=0.40，P=0.04）。KDR 1719 TT 基因型个体发生 HIV 疾病进展的风险更高（OR=2.31，P=0.23）。KDR 1719 TT 基因型个体在饮酒者中发生肝毒性的脆弱性更高（OR=2.57，P=0.23）。KDR 1719 TT 基因型个体在接受奈韦拉平且饮酒的个体中发生肝毒性及其严重程度的风险更高（OR=2.47，P=0.24；OR=5.42，P=0.42）。在多变量分析中，接受包含奈韦拉平的 ART 的肝毒性患者与肝毒性严重程度相关（OR=4.82，P=0.002）。总之，KDR 1719 TT 基因型和 AT 单倍型可能增加肝毒性及其严重程度的风险。AA 单倍型可能对降低发生肝毒性的风险有影响。
