Metabolic Syndrome: An Overview on Its Genetic Associations and Gene-Diet Interactions.

Metabolic syndrome (MetS) is a cluster of cardiometabolic risk factors that includes central obesity, hyperglycemia, hypertension, and dyslipidemias and whose inter-related occurrence may increase the odds of developing type 2 diabetes and cardiovascular diseases. MetS has become one of the most studied conditions, nevertheless, due to its complex etiology, this has not been fully elucidated. Recent evidence describes that both genetic and environmental factors play an important role on its development. With the advent of genomic-wide association studies, single nucleotide polymorphisms (SNPs) have gained special importance. In this review, we present an update of the genetics surrounding MetS as a single entity as well as its corresponding risk factors, considering SNPs and gene-diet interactions related to cardiometabolic markers. In this study, we focus on the conceptual aspects, diagnostic criteria, as well as the role of genetics, particularly on SNPs and polygenic risk scores (PRS) for interindividual analysis. In addition, this review highlights future perspectives of personalized nutrition with regard to the approach of MetS and how individualized multiomics approaches could improve the current outlook.

mtDNA haplogroup A enhances the effect of obesity on the risk of knee OA in a Mexican population.

To evaluate the influence of mitochondrial DNA haplogroups on the risk of knee OA in terms of their interaction with obesity, in a population from Mexico. Samples were obtained from (n = 353) knee OA patients (KL grade ≥ I) and (n = 364) healthy controls (KL grade = 0) from Mexico city and Torreon (Mexico). Both Caucasian and Amerindian mtDNA haplogroups were assigned by single base extension assay. A set of clinical and demographic variables, including obesity status, were considered to perform appropriate statistical approaches, including chi-square contingency tables, regression models and interaction analyses. To ensure the robustness of the predictive model, a statistical cross-validation strategy of B = 1000 iterations was used. All the analyses were performed using boot, GmAMisc and epiR package from R software v4.0.2 and SPSS software v24. The frequency distribution of the mtDNA haplogroups between OA patients and healthy controls for obese and non-obese groups showed the haplogroup A as significantly over-represented in knee OA patients within the obese group (OR 2.23; 95% CI 1.22-4.05; p-value = 0.008). The subsequent logistic regression analysis, including as covariate the interaction between obesity and mtDNA haplogroup A, supported the significant association of this interaction (OR 2.57; 95% CI 1.24-5.32; p-value = 0.011). The statistical cross-validation strategy confirmed the robustness of the regression model. The data presented here indicate a link between obesity in knee OA patients and mtDNA haplogroup A.

FGF21 serum levels are related to insulin resistance, metabolic changes and obesity in Mexican people living with HIV (PLWH).

BACKGROUND: Antiretroviral therapy has significantly improved prognosis in treatment against HIV infection, however, prolonged exposure is associated to cardiovascular diseases, lipodystrophy, type 2 diabetes, insulin resistance, metabolic alteration, as obesity which includes the accumulation of oxidative stress in adipose tissue. FGF21 is a peptide hormone that is known to regulate glucose and lipid metabolism. FGF21 is expressed and secreted primarily in the liver and adipose tissue, promoting oxidation of glucose/fatty acids and insulin sensitivity. Alterations in FGF21 may be associated with the development of insulin resistance, metabolic syndrome and cardiovascular disease. We hypothesized that FGF21 protein levels are associated with metabolic abnormalities, placing special attention to the alterations in relation to the concurrence of overweight/obesity in people living with HIV (PLWH). DESIGN: Serum FGF21 was analyzed in 241 subjects, 160 PLWH and 81 unrelated HIV-uninfected subjects as a control group. Clinical records were consulted to obtain CD4+ cell counting and number of viral RNA copies. Serum FGF21 levels were tested for correlation with anthropometric and metabolic parameters; glucose, cholesterol, HDL, LDL, VLDL, triglycerides, insulin and indexes of atherogenesis and insulin resistance (HOMA). RESULTS: The participants were classified into four groups: (i) PLWH with normal weight, (ii) PLWH with overweight/obesity, (iii) HIV-uninfected with normal weight, and (iv) HIV-uninfected with overweight/obesity. Insulin levels were higher in normal-weight PLWH than in the HIV-uninfected group but not statistically significant, however, for the overweight/obesity PLWH group, insulin levels were significantly higher in comparison with the other three groups (p<0.0001). For FGF21, serum levels were slightly higher in the overweight/obesity groups in both patients and controls. In HIV-infected subjects, FGF21 levels showed a strong positive correlation with triglycerides, insulin levels and insulin resistance with a p-value <0.0001. In the seronegative group, FGF21 was only correlated with weight and waist circumference, showing an important association of FGF21 levels with the degree of obesity of the individuals. CONCLUSION: Insulin resistance and FGF21 elevations were observed in overweight-obese PLWH. FGF21 elevation could be viewed as a compensation mechanism as, in the control group, FGF21 correlations appeared to be confined to weight and waist circumference. This can be explained based on the action of FGF21 promoting the uptake of glucose in adipose tissue. In PLWH, FGF21 was low, possibly as a result of a change in adiposity leading to a metabolic disruption.

Analyses of the Genetic Polymorphisms rs3740199 and rs1871054 of the ADAM12 Gene and the Alleles at the rs2073508 Loci of the TGFB1 Gene and Their Contribution to Susceptibility to Primary Knee Osteoarthritis.

Aims: To analyze the association of polymorphisms in the ADAM12 (rs3740199 and rs1871054) and TGFB1 (rs2073508) genes with knee osteoarthritis (KOA) in a population from northern Mexico. Methods: A total of 296 individuals were included in the study. Primary KOA was confirmed according to the criteria established by the American College of Rheumatology. A real-time PCR-based DNA genotyping method was used to evaluate the rs3740199, rs1871054, and rs2073508 polymorphisms in 132 cases and 164 controls. Results: Our results demonstrate that the ADAM12 rs3740199 polymorphism was significantly associated with primary KOA under the recessive model (p = 0.036). However, after performing a multinomial logistic regression model, no significant association was found (p = 0.722). Furthermore, no associations for the rs1871054 and rs2073508 polymorphisms were observed in this study. Conclusion: These findings suggest that polymorphisms within the ADAM12 and TGFB1 genes may not have a significant influence on primary KOA susceptibility in the Mexican Mestizo population; however, inclusion of other ethnic groups and a larger sample size are needed to more fully analyze the role of these polymorphisms with KOA risk.

Cartilage Oligomeric Matrix Protein Levels in Type 2 Diabetes Associated with Primary Knee Osteoarthritis Patients.

AIMS: (1) To evaluate the association between type 2 diabetes mellitus (T2D) and primary knee osteoarthritis (KOA); and (2) to compare synovial fluid (SF) cartilage oligomeric matrix protein (COMP) concentrations and glycemic control parameters in patients with T2D, with and without primary KOA. METHODS: A total of 231 individuals were included in this study. Primary KOA was confirmed according to the criteria established by the American College of Rheumatology. The presence of T2D was determined by medical history. In addition, fasting plasma glucose and glycated hemoglobin were analyzed to confirm diabetic and nondiabetic status. RESULTS: Our results showed an association between T2D and primary KOA after covariate adjustments (OR = 3.755, p = 0.000024, 95% CI: 2.033-6.934). In addition, SF COMP levels were significantly higher in T2D groups with and without primary KOA (p = 0.00035; p = 0.001 respectively) when compared to nonT2D controls. CONCLUSION: This study suggests a strong association between T2D and primary KOA; in addition, the presence of T2D may have an influence in SF COMP levels in subjects with and without primary KOA. The glycemic control parameters and duration of diabetes may be useful as an indirect indicator of SF COMP levels to prevent the effects of chronic exposure to hyperglycemia and subsequent damage to the articular cartilage.