Common Variants of the Liver Fatty Acid Binding Protein Gene Influence the Risk of Type 2 Diabetes and Insulin Resistance in Spanish Population

SummaryThe main objective was to evaluate the association between SNPs and haplotypes of the FABP1-4 genes and type 2 diabetes, as well as its interaction with fat intake, in one general Spanish population. The association was replicated in a second population in which HOMA index was also evaluated.Methods1217 unrelated individuals were selected from a population-based study [Hortega study: 605 women; mean age 54 y; 7.8% with type 2 diabetes]. The replication population included 805 subjects from Segovia, a neighboring region of Spain (446 females; mean age 52 y; 10.3% with type 2 diabetes). DM2 mellitus was defined in a similar way in both studies. Fifteen SNPs previously associated with metabolic traits or with potential influence in the gene expression within the FABP1-4 genes were genotyped with SNPlex and tested. Age, sex and BMI were used as covariates in the logistic regression model.ResultsOne polymorphism (rs2197076) and two haplotypes of the FABP-1 showed a strong association with the risk of DM2 in the original population. This association was further confirmed in the second population as well as in the pooled sample. None of the other analyzed variants in FABP2, FABP3 and FABP4 genes were associated. There was not a formal interaction between rs2197076 and fat intake. A significant association between the rs2197076 and the haplotypes of the FABP1 and HOMA-IR was also present in the replication population.ConclusionsThe study supports the role of common variants of the FABP-1 gene in the development of type 2 diabetes in Caucasians

Association between AT C573T polymorphism and cardiovascular risk factors in myocardial infarction

Background: Polymorphisms in the AT1 gene have been associated with various parameters related to the pathogenesis of cardiovascular diseases and to myocardial infarction. This study analyzed the relationship between two polymorphisms of the angiotensin II AT-1 receptor gene (AT1_1166 and AT1_573) and the risk of ischemic heart disease by studying their association with several cardiovascular risk factors. Methods: The sample population comprised 356 subjects: 174 patients who had survived myocardial infarction (61.01 ± 8.15 years), and 182 age- and gender-matched controls (mean age of 60.25 ± 9.43). The polymorphisms of the angiotensin II AT1-receptor gene (C573T and A1166C) were studied by polymerase chain reaction and DNA restriction analysis. We compared the patients' genetic polymorphism with their risk of ischemic heart disease. Results: The A1166C polymorphism did not show any significant differences between the groups. However, with respect to C573T, genotypes tended to differ significantly between cases and controls in the CC and TT types, remaining significant when the CC and CT+TT were grouped. Through analysis of the fit of various multivariate models, we found that the CC genotype is a risk factor for myocardial infarction. This risk remains significant after being adjusted for gender, age, homeostasis model assessment, and anthropometric variables. Conclusions: There is a relationship between the C573T polymorphism and the pathogenesis of myocardial infarction that seems to be due to its relationship with some risk factors. However, given the multifactorial nature of this pathology, further studies are needed to confirm the evidence that we report herein

GENOMIC AND METABOLOMIC PROFILE ASSOCIATED TO CLUSTERING OF CARDIO-METABOLIC RISK FACTORS

the sample included individuals older than 18 years in the absence of serious concomitantdisease or psychiatric disorder, which could interfere with the study. All the subjectsincluded were white, living in an area with a low immigration rate.<br>The study included the assessment of anthropometric measurements, blood pressure,  glycaemia, lipid profile and smoking status as well as personal and familial information<br>about cardiovascular risk factors and disease. Cardiometabolic risk factors were iidentified, according to the ATPIII criteria used for MS ], and MS was defined by the presence of three or more of the following components: 1) high waist circumference(men ≥ 102cm; women ≥88 cm); 2) high triglycerides (≥150mg/dL); 3) low HDL<br>cholesterol (men ≥ 40mg/dL; women ≥50mg/dL); 4) high blood pressure (systolic blood<br>pressure ≥130 mmHg and/or diastolic blood pressure ≥ 85 mmHg or being on<br>antihypertensive medications) and 5) high fasting glucose (≥ 110 mg/dL or being on drug treatment for elevated glucose). The subjects were divided into three groups:<br>Group 1 comprised of 617 subjects with less than two risk criteria of the ATPIIguideline; Group 2 comprised of 295 subjects with 2 risk factors and Group 3 comprised of 283 subjects with 3 or more of the criteria, which is considered to be MS.Weight was assessed with precise scales while the individuals were without shoes and<br>wearing light clothing. Height was determined in a similar way. Body mass index (BMI) was calculated using the following formula "weight (kg)/height2 (m)". Glucose<br>and lipid profile was measured in blood samples obtained with a mean of 3 hoursfasting (range 0-17). Basic serum biochemistry and lipid profile.Differences in the 28 metabolite values for each SNP in patients from Group 1 and Group 3 of each genotype were calculated. Finally, the metabolic profile and the most relevant metabolites of 5<br>genotype and allele were compared between patients from Group 1 and Group 3. The data were co-variated with respect to age, sex  and smoking status. Bonferroni correctionwas applied in all the analysis<br><br