The role of MTHFR gene in multiple myeloma.
Case-control studies investigating associations between multiple myeloma (MM) and the C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) have provided controversial results. In an attempt to interpret these results, a meta-analysis of all available studies was performed. In the meta-analysis the pooled odds ratios (OR) were estimated using fixed effects (FE) and random effects (RE) models. The heterogeneity between studies, the sources of potential bias and the consistency of genetic effects across ethnicities were explored. Cumulative meta-analysis was also performed. The meta-analysis revealed non-significant heterogeneity between studies (Pq > or = 0.65). The dominant model for the effect of 677T allele produced significant association overall [FE OR = 1.23 (1.04-1.47)] and in Caucasians [FE OR = 1.54 (1.14-2.08)], but not in East Asians [FE OR = 1.05 (0.82-1.34)]. Although the cumulative meta-analysis for the dominant model of 677T allele showed a downward trend of RE OR for the period 2000-2007, the association still remained significant. Analysis of the A1298C polymorphisms revealed lack of association both in Caucasians and in East Asians. There is an indication of potential bias: a differential magnitude of effect in large versus small studies emerged. In conclusion, the accumulated evidence indicated an association between MTHFR C677T polymorphism and MM in Caucasians under a dominant model.
Zintzaras
Elias
E
Department of Biomathematics, University of Thessaly School of Medicine, Papakyriazi 22, 41222, Larissa, Greece. zintza@med.uth.gr.|Center for Clinical Evidence Synthesis, The Institute for Clinical Research and Health Policy Studies, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, USA. zintza@med.uth.gr.
Giannouli
Stavroula
S
Department of Pathophysiology, University of Athens School of Medicine, Athens, Greece.
Rodopoulou
Paraskevi
P
Department of Biomathematics, University of Thessaly School of Medicine, Papakyriazi 22, 41222, Larissa, Greece.
Voulgarelis
Michael
M
Department of Pathophysiology, University of Athens School of Medicine, Athens, Greece.
D000483:Alleles; D015982:Bias; D005260:Female; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008957:Models, Genetic; D009101:Multiple Myeloma / Q000201:enzymology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012680:Sensitivity and Specificity; D044465:White People / Q000235:genetics
D042965:Methylenetetrahydrofolate Reductase (NADPH2)