Errigo Alessandra, Bitti Angela, Galistu Franca, Salis Roberta, Pes Giovanni Mario, Dore Maria Pina
Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy.
Laboratory of Azienda Ospedaliero-Universitaria, 07100 Sassari, Italy.
Antioxidants (Basel). 2023 Jan 31;12(2):334. doi: 10.3390/antiox12020334.
Recent studies suggest that X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency entails a proinflammatory state that may increase the risk of several disease conditions. However, it is not clear how this relates to the degree of enzyme insufficiency and, in heterozygous females, to skewed inactivation of the X chromosome. This study aimed to (i) investigate the enzyme activity in a cohort of 232 subjects (54.3% females) from Northern Sardinia, Italy, further stratified into three subgroups (G6PD normal, partial deficiency and total deficiency); (ii) measure the levels of some non-specific inflammatory markers, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and those derived from cell counts, such as neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) and platelet-to-lymphocyte ratio (PLR), in relation to the underlying molecular defect and X inactivation. G6PD activity was measured in red blood cells according to G6PD/6PGD ratio, and X-chromosome inactivation was assessed by the HUMARA method. Overall, ESR was increased in males with total deficiency compared with normal males (15.0 ± 7.2 vs. 11.9 ± 6.2, = 0.002, Tukey's test), albeit not in males with partial deficiency. High-sensitivity CRP was slightly increased in males with total deficiency, compared to males with normal G6PD activity (5.96 ± 3.39 vs. 3.95 ± 2.96, = 0.048). In females, neither marker showed significant differences across the subgroups. MLR was significantly and progressively increased from normal to totally deficient subjects with intermediate values in partially deficient subjects (0.18, 0.31 and 0.37, ANOVA = 0.008). The NLR and PLR were not different in the three subgroups. Our findings show that G6PD deficiency may be associated with a proinflammatory profile, especially in elderly females, and worsened by the concomitant asymmetric inactivation of the X chromosome.
近期研究表明，X连锁葡萄糖-6-磷酸脱氢酶（G6PD）缺乏会导致一种促炎状态，这可能会增加多种疾病的发病风险。然而，目前尚不清楚这与酶不足的程度有何关联，以及在杂合子女性中与X染色体的偏态失活有何关系。本研究旨在：（i）调查来自意大利撒丁岛北部的232名受试者（54.3%为女性）队列中的酶活性，进一步分为三个亚组（G6PD正常、部分缺乏和完全缺乏）；（ii）测量一些非特异性炎症标志物的水平，如红细胞沉降率（ESR）、C反应蛋白（CRP），以及那些源于细胞计数的指标，如中性粒细胞与淋巴细胞比值（NLR）、单核细胞与淋巴细胞比值（MLR）和血小板与淋巴细胞比值（PLR），并分析其与潜在分子缺陷和X染色体失活的关系。根据G6PD/6PGD比值测定红细胞中的G6PD活性，并通过HUMARA方法评估X染色体失活情况。总体而言，与正常男性相比，完全缺乏的男性ESR升高（15.0±7.2 vs. 11.9±6.2，P = 0.002，Tukey检验），而部分缺乏的男性则未升高。与G6PD活性正常的男性相比，完全缺乏的男性高敏CRP略有升高（5.96±3.39 vs. 3.95±2.96，P = 0.048）。在女性中，这两种标志物在各亚组之间均无显著差异。MLR从正常受试者到完全缺乏受试者显著且逐渐升高，部分缺乏受试者的值处于中间水平（分别为0.18、0.31和0.37，方差分析P = 0.008）。NLR和PLR在三个亚组中无差异。我们的研究结果表明，G6PD缺乏可能与促炎状态相关，尤其是在老年女性中，并且会因X染色体的伴随不对称失活而恶化。
