BACKGROUND:Alterations in levels of 25-hydroxyvitamin D have been associated with the risk of thyroid disease. This study uses Mendelian randomization (MR) to infer the possible causal association of 25-hydroxyvitamin D with hypothyroidism. METHODS:We performed two-sample MR using the summary statistics data from genome-wide association studies (GWAS) from populations with European ancestry to infer the causality of genetically controlled levels of 25-hydroxyvitamin D on the risk of hypothyroidism, Hashimoto's thyroiditis, and biochemical parameters of thyroid diseases. The inverse-variance-weighted (IVW) method was used as the primary method to calculate the combined effect of all SNPs. Other methods were adopted to evaluate the stability and reliability of the results. Comprehensive sensitivity analyses were conducted to ensure that none of the MR analysis's primary assumptions were violated. RESULTS:The results of the IVW analysis revealed a significant causal association between higher levels of 25-hydroxyvitamin D and lower risk of hypothyroidism (beta = -0.197, 95% CI [-0.301, -0.093]; SE = 0.053, Pbeta = 2.256 × 10-4) as well as increased levels of free T4 (beta = 0.204, 95% CI [0.094, 0.305]; SE = 0.056, Pbeta = 3.0506 × 10-4). On the other hand, no significant causality was determined for higher levels of 25-hydroxyvitamin D in association with Hashimoto's thyroiditis (beta = -0.047, 95% CI [-0.245, 0.151], p = 0.641) and TSH levels (IVW method: beta = -0.030, SE = 0.034, 95% CI [-0.097, 0.038]; P = 0.392). CONCLUSION:The results of this two-sample MR study provide evidence supporting the potential of 25-hydroxyvitamin D supplementation in reducing the risk of hypothyroidism.
Background In 2019, cardiovascular disease (CVD) was the primary cause of death worldwide, responsible for approximately 18.6 million fatalities, with its prevalence and incidence continuing to rise. In Iran, CVD accounts for 46.04% of all deaths, with demographic aging and sedentary lifestyles exacerbating the burden. This study evaluated the impact of metabolic risk factors and their trends on CVD development in an Iranian cohort. Methods In accordance with the Tehran Lipid and Glucose Study (TLGS), this longitudinal study included 1872 adults aged 40–79 years without prior CVD at baseline. The participants were selected through multistage random cluster sampling from 1999–2018. Data were collected on demographic, lifestyle, and metabolic factors, with laboratory analyses conducted via standardized protocols. Generalized estimating equations (GEEs) were used to assess age- and sex-adjusted trends of metabolic indicators. Results Over the 10-years of follow-up, 117 participants (6.3%) developed incident cardiovascular disease (CVD). Baseline CVD cases presented increased age, weight, blood pressure, fasting glucose, and lipid levels, and diabetes incidence. SBP showed consistent divergence between groups, while FPG and TyG demonstrated earlier separation in age- and sex-adjusted models that was attenuated after additional adjustment for treatment and lifestyle covariates. Conclusions Longitudinal trends of metabolic risk factors, particularly SBP, FPG, and the TyG index, were associated with incident CVD years before clinical onset and may serve as early predictive risk markers, with SBP showing the most consistent separation between groups. These findings emphasize the importance of early detection and preventive strategies targeting metabolic risk factors. Lifestyle modifications can significantly mitigate CVD risk, underscoring the utility of longitudinal data in understanding risk factor heterogeneity and disease progression. Greater attention should be given to trends with unstable cardiometabolic risk factors.
We conducted the Mendelian Randomization (MR) analysis to investigate the causal relationship between serum saturated fatty acids (SFAs) and the risk of heart stroke (HS). The MRC-IEU Consortium provided summary statistics datasets related to SFAs, encompassing 64,979 individuals of European descent. Genetic variants associated with HF were identified using a GWAS dataset comprising 461,880 participants (cases = 7,055, controls = 454,825) of European descent from the UK Biobank. Generalized summary Mendelian Randomization (GSMR) assessed the potential association. Additionally, we performed a two-sample Mendelian Randomization (TSMR). The odds ratio (OR) with 95
Colorectal cancer (CRC) is a type of cancer with a high recurrence rate. Studies are in the progress to identify effective treatments for CRC patients. We aimed to compare the expression of programmed death-ligand 1 (PD-L1) and anaplastic lymphoma kinase (ALK) in stages III and IV CRC patients and evaluate the clinicopathological significance associated with their expression. A total of 169 stages III and IV CRC specimens was tested for ALK (D5F3) and PD-L1 (SP142 and SP263) expression using immunohistochemistry on formalin-fixed paraffin-embedded specimens. Clinicopathological characteristics were obtained through a review of the medical records and hematoxylin and eosin slides. Expression of PD-L1 SP142 and PD-L1 SP263 was detected in 17.8% and 28.4% of CRC patients, respectively. ALK D5F3 expression was detected in 4 cases. PD-L1 SP142 expression was significantly correlated with tumor site and serum carcinoembryonic antigen (CEA) level. PD-L1 SP263 expression was associated with serum tumor marker level and tumor-infiltrating lymphocytes. In univariate analysis, PD-L1 expression was correlated with shorter survival in CRC patients. PD-L1 SP263 expression was an independent indicator of shorter survival in multivariate analysis. PD-L1 expression was associated with poor prognostic factors, including shorter survival. Further investigation is needed to understand the mechanisms of the association between PD-L1 expression and unfavorable CRC prognosis.
Background and Objectives: The association between the consumption of dairy products and the risk of cardiovascular disease (CVD) is not well-known yet. Here, we aimed to determine the potential effects of total intake and subtypes of dairy products on the development of CVD in an Iranian adult population. Methods: Among adult participants of the third phase of the Tehran Lipid and Glucose Study (TLGS), after excluding those with incomplete dietary, biochemical and anthropometric data, and those who had CVD events at baseline, 2635 adults were selected and followed up till the sixth phase of the TLGS. Baseline dietary intakes were evaluated using a validated food frequency questionnaire with 168 items. There was no significant difference between the baseline characteristics of participants who did not complete the FFQ and those of the total population in the third phase of the TLGS. Finally, the risk of CVD events after adjusting for potential confounding variables was evaluated across the tertile categories of dairy products using the Cox proportional hazard regression models. Results: During a 10.6-year follow-up, the incidence rate of CVD was 6.5%. After adjusting for confounding factors, there was no significant association between CVD risk and total dairy, low-fat and high-fat dairy, fermented and non-fermented dairy products, high- and low-fat milk, high- and low-fat yogurt, cheese, and cream cheese, as well as ice cream. Conclusion: According to numerous evidence in previous studies that revealed there is no association between the consumption of dairy products, and CVD risk, independent of high-fat or low-fat dairy products. Hence, it is vital to reconsider dietary recommendations on lowering the intake of high-fat dairy products for the prevention of CVD.
