Oussalah Abderrahim, Levy Julien, Filhine-Trésarrieu Pierre, Namour Fares, Guéant Jean-Louis
Department of Molecular Medicine and Personalized Therapeutics.
Department of Biochemistry, Molecular Biology, Nutrition, and Metabolism, and.
Am J Clin Nutr. 2017 Oct;106(4):1142-1156. doi: 10.3945/ajcn.117.156349. Epub 2017 Aug 16.
Vitamin B-12 (cobalamin) deficiency may produce severe neurologic and hematologic manifestations. Approximately 20-25% of circulating cobalamin binds to transcobalamin 2 (TCN2), which is referred to as active vitamin B-12. The G allele of the c.776G>C (rs1801198) polymorphism has been associated with a lower plasma concentration of holotranscobalamin. However, genotype association studies on rs1801198 have led to conflicting results regarding its influence on one-carbon metabolism (OCM) markers or its association with pathologic conditions. We assessed the association of rs1801198 genotypes with OCM marker concentrations and primary risks of congenital abnormalities, cancer, and Alzheimer disease. We conducted a systematic review of the literature that was published from January 1966 to February 2017 and included all studies that assessed the association between rs1801198 and OCM markers or a pathologic condition. Thirty-four studies met the inclusion criteria. Subjects with the rs1801198 GG genotype had significantly lower concentrations of holotranscobalamin [standardized mean difference (SMD): -0.445 (95% CI: -0.673, -0.217; < 0.001); = 48.16% (95% CI: 0.00%, 78.10%; = 0.07)] and higher concentrations of homocysteine (European descent only) [SMD: 0.070 (95% CI: 0.020, 0.120; = 0.01); = 0.00% (95% CI: 0.00%, 49.59%; = 0.73)] than did subjects with the rs1801198 CC genotype. The meta-analysis on the association between rs1801198 and methylmalonic acid (MMA) lacked statistical power. No significant difference was observed regarding cobalamin, folate, and red blood cell folate. No significant association was observed between rs1801198 and primary risks of congenital abnormalities, cancer, or Alzheimer disease. Meta-analysis results indicate an influence of rs1801198 on holotranscobalamin and homocysteine concentrations in European-descent subjects. In addition, well-designed and -powered studies should be conducted for assessing the association between rs1801198 and MMA and clinical manifestations that are linked to a decreased availability of cobalamin. This review was registered at www.crd.york.ac.uk/prospero as CRD42017058504.
维生素B-12（钴胺素）缺乏可能会产生严重的神经和血液学表现。循环中的钴胺素约20-25%与转钴胺素2（TCN2）结合，后者被称为活性维生素B-12。c.776G>C（rs1801198）多态性的G等位基因与全转钴胺素的血浆浓度较低有关。然而，关于rs1801198的基因型关联研究在其对一碳代谢（OCM）标志物的影响或与病理状况的关联方面得出了相互矛盾的结果。我们评估了rs1801198基因型与OCM标志物浓度以及先天性异常、癌症和阿尔茨海默病的主要风险之间的关联。我们对1966年1月至2017年2月发表的文献进行了系统综述，纳入了所有评估rs1801198与OCM标志物或病理状况之间关联的研究。34项研究符合纳入标准。与rs1801198 CC基因型的受试者相比，rs1801198 GG基因型的受试者全转钴胺素浓度显著更低[标准化均值差（SMD）：-0.445（95%置信区间：-0.673，-0.217；P<0.001）；I² = 48.16%（95%置信区间：0.00%，78.10%；P = 0.07）]，而（仅欧洲血统）同型半胱氨酸浓度更高[SMD：0.070（95%置信区间：0.020，0.120；P = 0.01）；I² = 0.00%（95%置信区间：0.00%，49.59%；P = 0.73）]。关于rs1801198与甲基丙二酸（MMA）之间关联的荟萃分析缺乏统计学效力。在钴胺素、叶酸和红细胞叶酸方面未观察到显著差异。未观察到rs1801198与先天性异常、癌症或阿尔茨海默病的主要风险之间存在显著关联。荟萃分析结果表明rs1801198对欧洲血统受试者的全转钴胺素和同型半胱氨酸浓度有影响。此外，应开展设计良好且有足够效力的研究，以评估rs1801198与MMA以及与钴胺素可用性降低相关的临床表现之间的关联。本综述已在www.crd.york.ac.uk/prospero注册，注册号为CRD42017058504。
