Nishijima Takeshi, Hayashida Tsunefusa, Kurosawa Takuma, Tanaka Noriko, Oka Shinichi, Gatanaga Hiroyuki
AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
PLoS One. 2015 Nov 4;10(11):e0141931. doi: 10.1371/journal.pone.0141931. eCollection 2015.
To investigate whether single nucleotide polymorphisms (SNP) of drug transporter proteins for TDF is a risk factor for TDF-related renal function decrement.
This study investigated the association between 3 SNPs (ABCC2-24, 1249, and ABCB1 2677), which are shown to be associated with TDF-induced tubulopathy, and clinically important renal outcomes (>10ml/min/1.73m2 decrement in eGFR relative to baseline, >25% decrement in eGFR, and eGFR <60ml/min/1.73m2) in 703 HIV-1-infected Japanese patients who initiated TDF-containing antiretroviral therapy (ART). Genotyping was performed by allelic discrimination using TaqMan 5'-nuclease assays.
95% of the study patients were males and 66% were treatment-naïve, with median CD4 count of 249/μl, median baseline eGFR of 96ml/min/1.73m2 (IQR 84.6-109.2), and median exposure to TDF of 3.66 years (IQR 1.93-5.59). The frequencies of genotypes at -24, 1249 of ABCC2, and 2677 of ABCB1 were neither different between patients with decrement in eGFR of >10ml/min/1.73m2 and those without such decrement (ABCC2: -24, p = 0.53, 1249, p = 0.68; ABCB1: 2677, p = 0.74), nor between those without and with the other two renal outcomes (>25% decrement: ABCC2: -24, p = 0.83, 1249, p = 0.97, ABCB1: 2677, p = 0.40; eGFR <60ml/min/1.73m2: ABCC2: -24, p = 0.51, 1249, p = 0.81, ABCB1: 2677, p = 0.94). Logistic regression analysis showed that the risk genotype of the three SNPs were not associated with any of the three renal outcomes, respectively. Logistic regression model that applied either dominant, recessive, or additive model yielded the same results.
SNPs of the drug transporters for TDF are not associated with clinically important renal outcomes in patients who initiated TDF-containing ART.
研究替诺福韦（TDF）药物转运蛋白的单核苷酸多态性（SNP）是否为TDF相关肾功能减退的危险因素。
本研究调查了3个SNP（ABCC2 - 24、1249以及ABCB1 2677）与临床重要肾脏结局之间的关联，这些SNP已被证明与TDF诱导的肾小管病变有关。本研究纳入703例开始含TDF抗逆转录病毒治疗（ART）的HIV - 1感染日本患者，观察的临床重要肾脏结局包括（相对于基线，估算肾小球滤过率[eGFR]下降>10ml/min/1.73m²、eGFR下降>25%以及eGFR<60ml/min/1.73m²）。采用TaqMan 5' - 核酸酶分析通过等位基因鉴别进行基因分型。
95%的研究患者为男性，66%为初治患者，CD4细胞计数中位数为249/μl，基线eGFR中位数为96ml/min/1.73m²（四分位间距84.6 - 109.2），TDF暴露时间中位数为3.66年（四分位间距1.93 - 5.59）。eGFR下降>10ml/min/1.73m²的患者与未下降患者相比，ABCC2基因 - 24、1249位点以及ABCB1基因2677位点的基因型频率无差异（ABCC2： - 24，p = 0.53，1249，p = 0.68；ABCB1：2677，p = 0.74）；在未出现和出现其他两种肾脏结局的患者之间（eGFR下降>25%：ABCC2： - 24，p = 0.83，1249，p = 0.97，ABCB1：2677，p = 0.40；eGFR<60ml/min/1.73m²：ABCC2： - 24，p = 0.51，1249，p = 0.81，ABCB1：2677，p = 0.94）也无差异。逻辑回归分析表明，这3个SNP的风险基因型分别与这3种肾脏结局均无关联。采用显性、隐性或加性模型的逻辑回归模型均得出相同结果。
对于开始含TDF的ART治疗的患者，TDF药物转运蛋白的SNP与临床重要肾脏结局无关。
