RESUMO
Background: Observational studies have shown that micronutrients can affect the occurrence of frailty. However, it is not clear whether there is a causal relationship between the two. This study aimed to explore the causal relationship between circulating micronutrient levels and frailty risk using a two-sample Mendelian randomization (TSMR) approach. Methods: We gathered and screened instrumental variables (IVs) for six circulating micronutrients, including vitamin B12, vitamin B6, folate, vitamin C, vitamin D, and vitamin E, from published genome-wide association studies (GWAS) and the IEU OpenGWAS open database. Summary statistics for frailty were obtained from a GWAS meta-analysis, including the UK Biobank and TwinGene (N = 175,226). We performed two independent TSMR analyses and a meta-analysis based on the two independent MR estimates to assess the causal relationship between circulating micronutrientn and frailty. Results: Our study found, no causal relationship between genetically predicted vitamin D (ß = -0.059, p = 0.35), vitamin B6 (ß = 0.006, p = 0.80), vitamin E (ß = -0.011, p = 0.79), vitamin C (ß = -0.044, p = 0.06), vitamin B12 (ß = -0.027, p = 0.37), and folate (ß = 0.029, p = 0.17), with frailty. Conclusion: This study showed that these six micronutrients did not reduce the risk of developing frailty. However, we think it is necessary further to investigate the relationship and mechanisms between micronutrients and frailty using methods such as randomized controlled trials.
RESUMO
BACKGROUND: Numerous studies have sought associations between matrix metalloproteinase 9 (MMP-9) polymorphisms and breast cancer risk. However, these studies have yielded conflicting results. Hence, we performed an updated meta-analysis to clarify the effects of four MMP-9 gene polymorphisms (rs3918242, rs2250889, rs3787268, and rs17576) on breast cancer risk. METHODS: A comprehensive literature search for eligible studies was conducted in five electronic databases, including PubMed, Embase and Web of Science, up to March 1, 2020. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations in random-effects models. For the reduction of type I errors, a trial sequential analysis (TSA) was performed. RESULTS: Twenty-one studies (8813 breast cancer cases and 9323 controls) were included in the quantitative analysis. For rs3918242, the overall ORs were significant under allelic comparison (OR A vs. G = 1.34; 95% CI 1.03, 1.74, P = 0.028) and the recessive genetic model (OR AA vs. GG+GA = 1.40; 95% CI 1.06, 1.84, P = 0.016). For rs2250889, the ORs were significant under homozygote comparison (OR GG vs. CC = 2.57; 95% CI 1.22, 5.42, P = 0.013), heterozygote comparison (OR GC vs. CC = 2.48; 95% CI 1.17, 5.23, P = 0.018), and the dominant genetic model (OR GG+GC vs. CC = 2.53; 95% CI 1.23, 5.20, P = 0.012). No associations were observed for rs3787268 or rs17576. The subgroup analyses indicated that the risk effect of the rs3918242 A allele was observed only among Asians. TSA showed that the findings for rs3918242, rs3787268, and rs17576 were robust, but many more patients are needed before definitive conclusions can be made for rs2250889. CONCLUSION: Our meta-analysis suggests that MMP-9 rs3918242, but not rs3787268 and rs17576 polymorphisms, may be risk factors for breast cancer. The effect of rs2250889 needs further confirmation with a larger sample size.