DOES SLC11A2 GENE MUTATION ASSOCIATE WITH IRON-REFRACTORY IRON-DEFICIENCY ANEMIA AFTER BARIATRIC SURGERY?

ABSTRACT - BACKGROUND: After bariatric surgery, if there is iron-refractory iron-deficiency anemia (IRIDA) and does not respond to supplemental iron therapy, excluding other possible etiologies, genetic changes involved in iron metabolism should be considered. AIM: This study aimed to investigate the association of both mutations 1285G-C and 1246C-T, in the SLC11A2 gene, and the etiopathogenesis of anemia refractory to iron supplementation in patients undergoing bariatric surgery using Roux-en-Y gastric bypass (RYGB). METHODS: A case-control study was conducted, in which 100 patients were evaluated as Cases Group [subdivided into (i) with Anemia and (ii) without Anemia] and 100 individuals as Controls, comprising both sexes. Inherited and acquired causes of IRIDA were excluded. DNA was extracted from leukocytes of peripheral blood, and the regions that cover both mutations have been amplified by the molecular techniques such as polymerase chain reaction/restriction fragment length polymorphism. RESULTS: The 1285G-C mutation was not determined in any of the 400 alleles analyzed. Regarding the 1246C-T mutation, the wild CC genotype was found with a higher prevalence in the Control Group (34%) (OR 0.5475; 95%CI 0.2920-1.027; p=0.0827). The mutant TT genotype was found only in the Cases Group I (with Anemia) (13%). CONCLUSION: The results show the association between 1246C-T mutation, in the SLC11A2 gene, and the etiopathogenesis of IRIDA to iron supplementation in the evaluated sample. There are differences, at the molecular level, in patients with and without IRIDA after bariatric surgery using RYGB.

摘要 - 背景：减肥手术后若出现铁难治性缺铁性贫血（iron-refractory iron-deficiency anemia, IRIDA）且对补铁治疗无应答，在排除其他可能病因后，应考虑铁代谢相关的遗传变异。目的：本研究旨在探讨SLC11A2基因的1285G-C与1246C-T两种突变，与接受Roux-en-Y胃旁路术（Roux-en-Y gastric bypass, RYGB）的减肥手术患者补铁难治性贫血的发病机制之间的关联。方法：本研究为病例对照研究，纳入100例患者作为病例组[分为(i)合并贫血亚组及(ii)未合并贫血亚组]，另纳入100名男女兼具的个体作为对照组。排除铁难治性缺铁性贫血的遗传性与获得性病因。从外周血白细胞中提取DNA，采用聚合酶链反应-限制性片段长度多态性（polymerase chain reaction/restriction fragment length polymorphism, PCR-RFLP）等分子生物学技术扩增覆盖两种突变位点的区域。结果：在所分析的400个等位基因中，未检测到1285G-C突变。针对1246C-T突变，野生型CC基因型在对照组中的检出率更高（34%）（比值比OR=0.5475；95%置信区间CI：0.2920~1.027；P=0.0827）。突变型TT基因型仅在病例组I（合并贫血亚组）中检出（13%）。结论：本研究结果显示，SLC11A2基因的1246C-T突变与本次研究样本中铁剂难治性缺铁性贫血的发病机制存在关联。接受RYGB减肥手术后的铁难治性缺铁性贫血患者与非患者在分子水平上存在差异。