HIV-associated sensory neuropathy (HIV-SN) is a debilitating neurological complication of HIV infection potentiated by the antiretroviral drug stavudine. While stavudine is no longer used, HIV-SN now affects around 15% of HIV+ Indonesians. Here, we investigate whether polymorphisms within the P2X-block (P2X4R, P2X7R, CAMKK2) and/or ANAPC5 mark susceptibility to HIV-SN in this setting. As polymorphisms in these genes associated with HIV-SN in African HIV patients receiving stavudine, the comparison can identify mechanisms independent of stavudine. HIV patients who had never used stavudine (n = 202) attending clinics in Jakarta were screened for neuropathy using the AIDS Clinical Trials Group Brief Peripheral Neuropathy Screen. Open-array technology was used to type 48 polymorphisms spanning the four genes. Haplotypes were derived for each gene using fastPHASE. Haplogroups were constructed with median-joining methods. Multivariable models optimally predicting HIV-SN were based on factors achieving p < 0.2 in bivariate analyses. Minor alleles of three co-inherited polymorphisms in CAMKK2 (rs7975295*C, rs1560568*A, rs1132780*T) associated with a reduced prevalence of HIV-SN individually and after adjusting for lower CD4 T cell count and viremia (p = 0.0002, pseudo R2 = 0.11). The optimal model for haplotypes linked HIV-SN with viremia and lower current CD4 T cell count, plus CAMKK2 haplotypes 6 and 11 and P2X7R haplotypes 2 and 12 (p = 0.0002; pseudo R2 = 0.11). CAMKK2 haplogroup A (includes 16 haplotypes and all instances of rs7975295*C, rs1560568*A, rs1132780*T) associated with reduced rates of HIV-SN (p = 0.02, OR = 0.43 CI = 0.21-0.88). These findings support a protective role for these three alleles, suggesting a role in the pathogenesis of HIV-SN that is independent of stavudine.

中文翻译：

---

在未使用司他夫定治疗的HIV患者中，CAMKK2的多态性与易感神经病相关。

HIV相关的感觉神经病（HIV-SN）是抗逆转录病毒药物司他夫定增强的HIV感染的虚弱神经系统并发症。虽然不再使用司他夫定，但现在，HIV-SN影响约15％的HIV +印度尼西亚人。在这里，我们调查在这种情况下P2X区块（P2X4R，P2X7R，CAMKK2）和/或ANAPC5内的多态性是否标志着对HIV-SN的易感性。由于在接受司他夫定的非洲HIV患者中与HIV-SN相关的这些基因的多态性，该比较可以确定独立于司他夫定的机制。从未在雅加达就诊的从未使用过司他夫定（n = 202）的艾滋病毒患者使用AIDS临床试验小组简要外围神经病变筛查进行了神经病变筛查。开放式阵列技术用于跨越这四个基因的48种多态性。使用fastPHASE推导每个基因的单倍型。使用中位数连接方法构建单倍群。最佳预测HIV-SN的多变量模型基于双变量分析中达到p <0.2的因素。CAMKK2（rs7975295 * C，rs1560568 * A，rs1132780 * T）中三个共同遗传的多态性的次要等位基因，与单独降低HIV-SN的患病率有关，并针对较低的CD4 T细胞计数和病毒血症进行了调整（p = 0.0002，假性R2 = 0.11）。单体型的最佳模型将HIV-SN与病毒血症和较低的当前CD4 T细胞计数联系在一起，加上CAMKK2单体型6和11和P2X7R单体型2和12（p = 0.0002；伪R2 = 0.11）。CAMKK2单倍型A（包括16个单倍型以及rs7975295 * C，rs1560568 * A，rs1132780 * T的所有实例）与HIV-SN的发病率降低相关（p = 0.02，OR = 0.43 CI = 0.21-0.88）。