A meta-analysis of case-control studies that investigated the association between the C677T and/or A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and acute lymphoblastic leukemia (ALL) was carried out. Pooled odds ratios (OR) of various genetic contrasts of each polymorphism were estimated using random (RE) and fixed effects (FE) models. Pooled ORs for combined genotypes and haplotypes were estimated after adjustment for study effect using a log-linear model and the expectation-maximization algorithm in combination with log-linear modeling, respectively. The recessive model for allele 1298C produced a rather marginal association: RE OR: 0.67; 95% confidence interval (CI): 0.46-0.99 and FE OR: 0.64; 95% CI: 0.49-0.84. In Caucasians, the results of the recessive model for allele 1298C was consisted with a protective effect of ALL development: FE OR: 0.63; 95% CI: 0.46-0.87. In childhood ALL, according to the results of the allele contrast and the recessive model for 677T allele it was conceivable that a protective effect exist: RE OR = 0.74; 95% CI: 0.57-0.96 and RE OR: 0.69; 95% CI: 0.51-0.94, respectively. The combined genotypes produced significant pooled OR for the 677CC/1298CC relative to 677CC/1298AA (OR: 0.54; 95% CI: 0.36-0.80). The haplotype 677C/1298C might be more protective to ALL relative to haplotype 677C/1298A (OR: 0.77; 95% CI: 0.61-0.97). When studies not in Hardy-Weinberg equilibrium (HWE) were corrected to account for departures from HWE, then, the pattern of results remained the same. Overall, there is high heterogeneity between the studies in both polymorphisms. A differential magnitude of effect in large versus small studies and alteration of early extremes effects existed.

The available data suggest differences in the course of type 2 diabetes mellitus (T2DM) between men and women, influenced by the distinguishing features of the sex. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are a relatively new class of antidiabetic drugs that act by mimicking the function of endogenous glucagon-like peptide 1. They constitute valuable agents for the management of T2DM as, in addition to exerting a strong hypoglycemic action, they present cardiorenal protective properties, promote weight loss, and have a good safety profile, particularly with respect to the risk of hypoglycemia. Due to the precedent of studies having identified sexual dimorphic elements regarding the action of other antidiabetic agents, ongoing research has attempted to examine whether this is also the case for GLP-1 RAs. Until now, sex differences have been observed in the impact of GLP1-RAs on glycemic control, weight reduction, and frequency of adverse events. On the contrary, the question of whether these drugs differentially affect the two sexes with respect to cardiovascular risk and incidence of major adverse cardiovascular events remains under investigation. Knowledge of the potential sex-specific effects of these medications is extremely useful for the implementation of individualized therapeutic plans in the treatment of T2DM. This narrative review aims to present the available data regarding the sex-specific action of GLP-1 RAs as well as to discuss the potential pathophysiologic mechanisms explaining these dissimilarities.

BackgroundFocal adhesion (FA) family genes have been studied as candidate genes for osteoporosis, but the results of genetic association studies (GASs) are controversial. To clarify these data, a systematic assessment of GASs for FA genes in osteoporosis was conducted.MethodsWe developed Cumulative Meta-Analysis of GAS-OSTEOporosis (CUMAGAS-OSTEOporosis), a web-based information system that allows the retrieval, analysis and meta-analysis (for allele contrast, recessive, dominant, additive and codominant models) of data from GASs on osteoporosis with the capability of update. GASs were identified by searching the PubMed and HuGE PubLit databases.ResultsData from 72 studies involving 13 variants of 6 genes were analyzed and catalogued in CUMAGAS-OSTEOporosis. Twenty-two studies produced significant associations with osteoporosis risk under any genetic model. All studies were underpowered (<50%). In four studies, the controls deviated from the Hardy-Weinberg equilibrium. Eight variants were chosen for meta-analysis, and significance was shown for the variants collagen, type I, α1 (COL1A1) G2046T (all genetic models), COL1A1 G-1997T (allele contrast and dominant model) and integrin β-chain β3 (ITGB3) T176C (recessive and additive models). In COL1A1 G2046T, subgroup analysis has shown significant associations for Caucasians, adults, females, males and postmenopausal women. A differential magnitude of effect in large versus small studies (that is, indication of publication bias) was detected for the variant COL1A1 G2046T.ConclusionThere is evidence of an implication of FA family genes in osteoporosis. CUMAGAS-OSTEOporosis could be a useful tool for current genomic epidemiology research in the field of osteoporosis.

Given the limitations of available evidence, more studies are required before reaching definite conclusions about the effects of OF on human health.