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Purpose: The aim of this study was to investigate the causal relationships between circulating cell traits and risk of renal disorders. Methods: We applied a comprehensive two-sample Mendelian randomization (MR) analysis. Single nucleotide polymorphisms (SNPs) from publicly available genome-wide association studies (GWAS) databases were utilized. Genetically predicted instrumental variables of human blood cell traits were extracted from Blood Cell Consortium (BCX) while data on renal diseases was obtained from Finngen consortium. The primary MR analysis was conducted using the inverse variance weighted (IVW) method, with the weighted median (WM) and MR-Egger models used as additional methods. Sensitivity analyses, including MR-PRESSO, radial regression and MR-Egger intercept were conducted to detect outliers and assess horizontal pleiotropy. We further utilized the leave-one-out analysis to assess the robustness of the results. Causal associations were considered significant based on false rate correction (FDR), specifically when the IVW method provided a pFDR < 0.05. Results: Our results demonstrated that both white blood cell (WBC) count (OR = 1.50, 95% CI = 1.10-2.06, pFDR = 0.033, pIVW = 0.011) and lymphocyte count (OR = 1.50, 95% CI = 1.13-1.98, pFDR = 0.027, pIVW = 0.005) were causally associated with a higher risk of IgA nephropathy. Furthermore, WBC count was identified as a significant genetic risk factor for renal malignant neoplasms (OR = 1.23, 95% CI = 1.06-1.43, pFDR = 0.041, pIVW = 0.007). Additionally, an increased level of genetically predicted eosinophils was found to be causally associated with a higher risk of diabetic nephropathy (OR = 1.21, 95% CI = 1.08-1.36, pFDR = 0.007, pIVW = 0.001). No evidence of pleiotropy was determined. Conclusion: Our findings provide evidence of causal associations of circulating WBC count, lymphocyte count and IgA nephropathy, WBC count and renal malignant neoplasms, and eosinophil count and diabetic nephropathy. These results have the potential to contribute to the development of novel diagnostic options and therapeutic strategies for renal disorders.
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INTRODUCTION: The aim of this meta-analysis was to summarize the evidence on the serum/plasma leptin concentrations in breast cancer (BC) patients, as well as the associations between leptin G-2548A gene polymorphisms and susceptibility to BC. MATERIAL AND METHODS: Potentially relevant studies about serum/plasma leptin levels and leptin G-2548A gene polymorphism were selected using the electronic databases PubMed, EMBASE and The Cochrane Library (from January 1 1995 to Jun 30 2017, no language restrictions). The potential sources of heterogeneity were assessed by the Q statistic and quantified using I2 ; publication bias was qualitatively assessed by funnel plot and quantitatively assessed by Egger's linear regression test. RESULTS: A total of 1141 articles were retrieved after database searches, and 27 studies with 9516 subjects (4542 BC patients/4974 controls) were finally included. The results indicated that BC patients had significantly higher leptin levels compared with healthy controls (SMD = 1.65, 95% CI: 1.21-2.09, p < 0.001), but there was no association between leptin G-2548A polymorphism and BC (OR = 1.05, 95% CI: 0.80-1.39, p = 0.722). Subgroup analyses demonstrated increased leptin levels in BC patients of different region, race, body mass index and waist circumference. CONCLUSIONS: Our results revealed a significantly higher leptin level in BC patients than in healthy controls, but no association between leptin G-2548A polymorphism and BC susceptibility was found.
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Genetic engineering of Lactococcus lactis to produce a heterologous protein may cause potential risks to the environment despite the industrial usefulness of engineered strains. To reduce the risks, we generated three auxotrophic recombinant L. lactis subsp. lactis IL1403 strains expressing a heterologous protein, BmpB, using thyA- and alr-targeting integration vectors: ITD (thyA(-)alr(+) bmpB(+)), IAD (thyA(+)alr(-)bmpB(+)), and ITDAD (thyA(-)alr(-) bmpB(+)). After construction of integration vectors, each vector was introduced into IL1403 genome. Integration of BmpB expression cassette, deletion of thyA, and inactivation of alr were verified by using PCR reaction. All heterologous DNA fragments except bmpB were eliminated from those recombinants during double crossover events. By using five selective agar plates, we also showed thymidine auxotrophy of ITD and ITDAD and D-alanine auxotrophy of IAD and ITDAD. In M17G and skim milk (SYG) media, the growth of the three recombinants was limited. In MRS media, the growth of IAD and ITDAD was limited, but ITD showed a normal growth pattern as compared with the wild-type strain (WT). All the recombinants showed maximal BmpB expression at an early stationary phase when they were cultivated in M17G supplemented with thymidine and D-alanine. These results suggest that auxotrophic recombinant L. lactis expressing a heterologous protein could be generated to reduce the ecological risks of a recombinant L. lactis.
