McDermid Joann M, van der Loeff Maarten F Schim, Jaye Assan, Hennig Branwen J, Bates Chris, Todd Jim, Sirugo Giorgio, Hill Adrian V, Whittle Hilton C, Prentice Andrew M
Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
Am J Clin Nutr. 2009 Jul;90(1):225-33. doi: 10.3945/ajcn.2009.27709. Epub 2009 May 27.
Iron-related genes and iron status may independently contribute to variable HIV outcomes. The nature of the biologically plausible gene-nutrient interaction remains unknown.
The objectives were to investigate whether iron-related genotypes and clinically abnormal iron status independently predict mortality in HIV and whether a gene-nutrient interaction exists.
Baseline plasma, DNA, and clinical data were obtained from 1362 HIV-seropositive Gambian adults followed for 11.5 y to ascertain all-cause mortality. Iron status was estimated on the basis of plasma iron, soluble transferrin receptor (sTfR), ferritin, transferrin, transferrin index, and log(sTfR/ferritin). One haptoglobin (HP) and 5 SLC11A1 (NRAMP1) polymorphisms were genotyped.
SLC11A1-SLC3 and CAAA polymorphisms were the best independent genetic predictors of mortality [adjusted mortality rate ratio (95% CI)]: SLC3:G/C = 0.59 (95% CI: 0.45, 0.85), CAAA:del/ins = 1.51 (95% CI: 1.10, 2.07). In an adjusted model that included all polymorphisms, SLC1:199/199, SLC1:other/other, SLC6a:A/A, and CAAA:del/ins were associated with significantly greater mortality, whereas Hp 2-1 and SLC3:G/C were protective. In unadjusted analyses, all biomarker concentrations were significantly associated with mortality. In an extension of previous findings, both low and elevated iron states were associated with mortality, but the nature of the risk was variable, with linear, inversely linear, and U-shaped associations depending on the biomarker. Mortality was significantly lower in HIV-2 than in HIV-1 infection in the presence of abnormal (low or elevated) iron status. A gene-iron interaction was detected (likelihood-ratio test P = 0.018); however, subject numbers restricted category-specific interpretation.
Iron-related genes, iron status, and their interaction predict mortality in HIV. These findings illustrate the complexity and uncertainty surrounding best practice for managing abnormal iron status and anemia during HIV infection and in regions with a high risk of infection.
铁相关基因和铁状态可能独立影响艾滋病病毒（HIV）感染的不同结局。生物学上合理的基因 - 营养相互作用的本质尚不清楚。
研究铁相关基因型和临床异常铁状态是否独立预测HIV感染者的死亡率，以及是否存在基因 - 营养相互作用。
从1362名HIV血清阳性的冈比亚成年人中获取基线血浆、DNA和临床数据，随访11.5年以确定全因死亡率。根据血浆铁、可溶性转铁蛋白受体（sTfR）、铁蛋白、转铁蛋白、转铁蛋白指数和log（sTfR/铁蛋白）评估铁状态。对一种触珠蛋白（HP）和5种溶质载体家族11成员A1（SLC11A1，又称NRAMP1）基因多态性进行基因分型。
SLC11A1 - SLC3和CAAA多态性是死亡率的最佳独立遗传预测指标[调整后的死亡率比（95%置信区间）]：SLC3：G/C = 0.59（95%置信区间：0.45，0.85），CAAA：del/ins = 1.51（95%置信区间：1.10，2.07）。在包含所有多态性的调整模型中，SLC1：199/199、SLC1：其他/其他、SLC6a：A/A和CAAA：del/ins与显著更高的死亡率相关，而Hp 2 - 1和SLC3：G/C具有保护作用。在未调整分析中，所有生物标志物浓度均与死亡率显著相关。在先前研究结果的扩展中，低铁状态和高铁状态均与死亡率相关，但风险性质各不相同，根据生物标志物的不同呈现线性、反线性和U形关联。在铁状态异常（低或高）的情况下，HIV - 2感染者的死亡率显著低于HIV - 1感染者。检测到基因 - 铁相互作用（似然比检验P = 0.018）；然而，样本数量限制了特定类别解释。
铁相关基因、铁状态及其相互作用可预测HIV感染者的死亡率。这些发现说明了在HIV感染期间以及高感染风险地区管理异常铁状态和贫血的最佳实践所面临的复杂性和不确定性。
