Asensi Victor, Rego Carolina, Montes A Hugo, Collazos Julio, Carton José A, Castro Mónica G, Alvarez Victoria, Fernández Cristina, Maradona José A, Valle-Garay Eulalia
Infectious Diseases and Molecular Genetics Sections, Hospital Central de Asturias, Oviedo, Spain.
Genet Med. 2008 Mar;10(3):215-23. doi: 10.1097/GIM.0b013e3181632713.
To evaluate the impact of acquired and inherited factors on the development of lipodystrophic syndrome in patients on highly active antiretroviral therapy.
Two hundred forty-three human immunodeficiency virus-infected Caucasians on highly active antiretroviral therapy were prospectively followed-up for 3 years. Eleven were naIve and 232 were on antiretrovirals (mean, 93.0 months +/- 43.8 months). Lipodystrophic syndrome was diagnosed clinically with a lipodystrophy severity grading scale. Polymorphisms of cytokines (IL-1beta, IL-6, TNF-alpha), TLR4, and NOS genes were genotyped.
Ninety (37%) patients developed lipodystrophic syndrome. The polymorphic T allele of the (+3954C/T) polymorphism of IL-1beta was less frequent in patients with lipodystrophic syndrome compared with those without (17.8% vs. 27.0%, P = 0.03). Factors significantly associated with lipodystrophic syndrome were time on stavudine (P < 0.001), use of stavudine (P = 0.001), absence of the T allele of the (+3954C/T) IL-1beta polymorphism (P = 0.02), acquired immune deficiency syndrome diagnosis (P = 0.005), nadir levels of CD4 (P = 0.003), and time on highly active antiretroviral therapy (P = 0.003). Of these factors, only the time on stavudine (hazard ratio [95% confidence intervals] 1.007 [1.001-1.013]), use of stavudine (1.678 [1.048-2.68]), and absence of the T allele of the IL-1beta (+3954C/T) polymorphism (0.569 [0.347-0.931]) were significantly associated with lipodystrophic syndrome by Cox regression.
Genotyping of the (+3954C/T) polymorphism of IL-1beta could be useful in patients starting highly active antiretroviral therapy, especially in potential users of stavudine, to predict their risk of developing lipodystrophic syndrome.
评估获得性和遗传性因素对接受高效抗逆转录病毒治疗的患者脂肪代谢障碍综合征发展的影响。
对243例接受高效抗逆转录病毒治疗的人类免疫缺陷病毒感染的白种人进行了为期3年的前瞻性随访。11例为初治患者，232例正在接受抗逆转录病毒治疗（平均93.0个月±43.8个月）。采用脂肪代谢障碍严重程度分级量表对脂肪代谢障碍综合征进行临床诊断。对细胞因子（IL-1β、IL-6、TNF-α）、TLR4和NOS基因的多态性进行基因分型。
90例（37%）患者发生脂肪代谢障碍综合征。与未发生脂肪代谢障碍综合征的患者相比，脂肪代谢障碍综合征患者中IL-1β（+3954C/T）多态性的多态性T等位基因频率较低（17.8%对27.0%，P = 0.03）。与脂肪代谢障碍综合征显著相关的因素包括司他夫定治疗时间（P < 0.001）、司他夫定的使用（P = 0.001）、IL-1β（+3954C/T）多态性T等位基因缺失（P = 0.02）、获得性免疫缺陷综合征诊断（P = 0.005）、CD4最低点水平（P = 0.003）以及高效抗逆转录病毒治疗时间（P = 0.003）。在这些因素中，通过Cox回归分析，只有司他夫定治疗时间（风险比[95%置信区间]1.007[1.001 - 1.013]）(^①)、司他夫定的使用（1.678[1.048 - 2.68]）以及IL-1β（+3954C/T）多态性T等位基因缺失（0.569[0.347 - 0.931]）与脂肪代谢障碍综合征显著相关。
对IL-1β（+3954C/T）多态性进行基因分型可能有助于开始接受高效抗逆转录病毒治疗的患者，尤其是司他夫定的潜在使用者，预测其发生脂肪代谢障碍综合征的风险。
(^①)原文此处可能是笔误，推测应为“风险比[95%置信区间]1.007[1.001 - 1.013]” ，实际翻译时按推测内容准确翻译，以保证译文逻辑通顺。
