José L. González-Sánchez

Prevalencia del síndrome metabólico (criterios del ATP-III). Estudio de base poblacional en áreas rural y urbana de la provincia de Segovia

Fundamento y objetivo Estimar la prevalencia del sindrome metabolico (SM) en areas rural y urbana de Segovia (Espana), segun los criterios del ATP-III (National Cholesterol Education Programs Adults Treatment Panel III Report) modificados. Sujetos y metodo Estudio transversal realizado con una muestra aleatoria y representativa formada por 809 individuos (un 46% varones) de 35 a 74 anos de edad residentes en areas rural y urbana de la provincia de Segovia (Espana). El periodo de estudio fue de enero de 2000 a enero de 2003. Resultados La prevalencia global del SM ajustada por edad y sexo fue del 17% (un 15,7% en varones y un 18,1% en mujeres) y no se observaron diferencias entre las poblaciones de las areas rural y urbana. La combinacion de componentes del SM mas frecuente, tanto en varones como en mujeres, fue la de obesidad abdominal, glucosa alterada en ayunas e hipertension arterial. La prevalencia de SM se asocio a la edad y a la obesidad en un modelo de regresion logistico multivariado. En otro modelo, la obesidad abdominal fue mas frecuente en los individuos con obesidad, definida por un indice de masa corporal de 30 kg/m2 o mayor, en aquellos con estudios secundarios, o con edad superior a 45 anos y en las mujeres residentes en el area rural. Conclusiones La prevalencia global ajustada por sexo/edad fue menor que la obtenida en otros estudios con los mismos criterios de definicion de SM (ATP-III), lo que induce a pensar en la existencia de diferencias geograficas en Espana. La obesidad abdominal fue el componente aislado del SM de mayor prevalencia en mujeres, mientras que la hipertension arterial lo fue en varones.

Variant rs9939609 in the FTO gene is associated with obesity in an adult population from Spain

Objective  Recently independent studies, including genome‐wide scans, have shown that variation in the fat mass and obesity associated gene (FTO) were significantly associated with obesity in populations of European origin.

The CAPN10 Gene Is Associated with Insulin Resistance Phenotypes in the Spanish Population

Cardiovascular disease is the leading cause of morbidity and mortality in the industrialized world. Familial aggregation of cardiovascular risk factors is a frequent finding, but genetic factors affecting its presentation are still poorly understood. The calpain 10 gene (CAPN10) has been associated with type 2 diabetes (T2DM), a complex metabolic disorder with increased risk of cardiovascular disease. Moreover, the CAPN10 gene has been associated with the presence of metabolic syndrome (MS) in T2DM and in polycystic ovary syndrome (PCOS). In this work, we have analysed whether the polymorphisms UCSNP44, -43, -19 and -63 are related to several cardiovascular risk factors in the context of MS. Molecular analysis of CAPN10 gene was performed in 899 individuals randomly chosen from a cross-sectional population-based epidemiological survey. We have found that CAPN10 gene in our population is mainly associated with two indicators of the presence of insulin resistance: glucose levels two hours after a 75-g oral glucose tolerance test (OGTT) and HOMA values, although cholesterol levels and blood pressure values are also influenced by CAPN10 variants. In addition, the 1221/1121 haplogenotype is under-represented in individuals that fulfil the International Diabetes Federation (IDF) diagnostic criteria for MS. Our results suggest that CAPN10 gene is associated with insulin resistance phenotypes in the Spanish population.

Sex and Body Mass Index Specific Regulation of Blood Pressure by CYP19A1 Gene Variants

Sexual dimorphism in blood pressure (BP) regulation has been observed both in humans and experimental animals, and estrogens have been shown to contribute to this epidemiological observation. A key enzyme in determining estrogen levels is aromatase cytochrome P450. The aim of this study was to evaluate the role of the gene encoding aromatase, CYP19A1, as an independent risk factor for hypertension and its relationship with systolic and diastolic BP measures. We genotyped 2 polymorphisms within the CYP19A1 gene, IVS4 rs11575899 and 3′UTR rs10046, in 3448 individuals. In quantitative analysis, we observed significant associations between the 2 polymorphisms and BP values in women, being these associations dependent on BMI and independent of menopause status. The case-control analysis revealed that the most prominent associations were found for nonobese women in diastolic hypertension (DHT): the IVS4_22 and 3′UTR_11 are risk genotypes (OR=1.61, P=0.027 and OR=1.59, P=0.012, respectively), whereas IVS4_11 and 3′UTR_22 genotypes have a protective effect against DHT (OR=0.63, P=0.009, and OR=0.61, P=0.020, respectively). Haplotype analysis confirmed the above associations: among nonobese women the haplotype 21 is overrepresented in hypertensive women (OR=1.33, P=0.004, for DHT and OR=1.25, P=0.026, for systolic hypertension, SHT) and, conversely, the haplotype 12 protects against hypertension (OR=0.78, P=0.015 for DHT and OR=0.82, P=0.04 for SHT). Our study has shown that the CYP19A1 gene may be involved in the genetic regulation of BP in women. This effect is dependent on BMI and independent of menopause status, suggesting that this action is mainly driven by aromatase activity in fat tissue.

Calpain-5 gene variants are associated with diastolic blood pressure and cholesterol levels

BackgroundGenes implicated in common complex disorders such as obesity, type 2 diabetes mellitus (T2DM) or cardiovascular diseases are not disease specific, since clinically related disorders also share genetic components. Cysteine protease Calpain 10 (CAPN10) has been associated with T2DM, hypertension, hypercholesterolemia, increased body mass index (BMI) and polycystic ovary syndrome (PCOS), a reproductive disorder of women in which isunlin resistance seems to play a pathogenic role. The calpain 5 gene (CAPN5) encodes a protein homologue of CAPN10. CAPN5 has been previously associated with PCOS by our group. In this new study, we have analysed the association of four CAPN5 gene variants(rs948976A>G, rs4945140G>A, rs2233546C>T and rs2233549G>A) with several cardiovascular risk factors related to metabolic syndrome in general population.MethodsAnthropometric measurements, blood pressure, insulin, glucose and lipid profiles were determined in 606 individuals randomly chosen from a cross-sectional population-based epidemiological survey in the province of Segovia in Central Spain (Castille), recruited to investigate the prevalence of anthropometric and physiological parameters related to obesity and other components of the metabolic syndrome. Genotypes at the four polymorphic loci in CAPN5 gene were detected by polymerase chain reaction (PCR).ResultsGenotype association analysis was significant for BMI (p ≤ 0.041), diastolic blood pressure (p = 0.015) and HDL-cholesterol levels (p = 0.025). Different CAPN5 haplotypes were also associated with diastolic blood pressure (DBP) (0.0005 ≤ p ≤ 0.006) and total cholesterol levels (0.001 ≤ p ≤ 0.029). In addition, the AACA haplotype, over-represented in obese individuals, is also more frequent in individuals with metabolic syndrome defined by ATPIII criteria (p = 0.029).ConclusionAs its homologue CAPN10, CAPN5 seems to influence traits related to increased risk for cardiovascular diseases. Our results also may suggest CAPN5 as a candidate gene for metabolic syndrome.

Association of ENPP1 (PC-1) K121Q polymorphism with obesity-related parameters in subjects with metabolic syndrome

Background  The metabolic syndrome (MS), a cluster of several metabolic disorders, is increasingly being recognized as a risk factor for cardiovascular disease. Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), originally described as a plasma cell allo‐antigen and named plasma cell membrane glycoprotein (PC‐1), is an inhibitor of insulin‐induced activation of the insulin receptor. The single nucleotide polymorphism (SNP) K121Q in the ENPP1 gene has been studied in relation to obesity, insulin resistance and other features of MS in several populations with conflicting results.

Common haplotypes of the C-reactive protein gene and circulating leptin levels influence the interindividual variability in serum C-reactive protein levels - The Segovia study

C-reactive protein (CRP) is a marker of systemic inflammation significantly associated with an increased risk of cardiovascular disease in the general population. The aim of our current work was to study those clinical and genetic variables potentially associated with interindividual variability in serum CRP levels. A random sample of 844 participants (450 women, mean age 55 years) from a study carried out on the general Spanish population (The Segovia Study) was studied. Our results showed that age, gender, waist circumference, leptin, impaired glucose tolerance and smoking were the clinical variables significantly associated with variations in serum CRP levels. Among those, leptin showed the strongest association, explaining 11% of the interindividual variability in circulating CRP levels (p<0.001). To study the effect of genetic variants on serum CRP levels, 10 SNPs within the CRP locus were genotyped in 756 participants. Four of these SNPs (rs1417938, rs1800947, rs1130864, rs1205) were significantly associated with CRP levels after adjustment for clinical variables. Among the common haplotypes inferred from eight SNPs, two (CCATGCCT, p=0.025; CTATCCTT, p=0.004) explained 2.9% of the total variation in serum CRP. The results here reported show that 2.9% of the total variation in circulating CRP levels seems to be explained by genetics variations within CRP locus. Furthermore, serum leptin levels are strongly associated with serum CRP levels in our Spanish population.

Is the plasminogen activator inhibitor-1 gene a candidate gene predisposing to hypertension? Results from a population-based study in Spain.

Background Studies in humans and mice suggest that plasminogen activator inhibitor-1 (PAI-1) might be a candidate gene for arterial hypertension. Our aims were to analyse whether the functional 4G/5G PAI-1 polymorphism represents a risk marker for the development of arterial hypertension regardless of hypertension-related metabolic variables. Methods Eight hundred and fifteen unrelated individuals (387 men, age 35–74 years) from a cross-sectional, population-based, epidemiological survey in the province of Segovia (Spain) were studied. Anthropometric/biochemical parameters – body mass index, waist circumference, diastolic and systolic blood pressures, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, fasting glucose, insulin, C-reactive protein, and PAI-1 levels – were analysed. The 4G/5G PAI-1 genotypes were established by restriction fragment length polymorphism. Insulin resistance was estimated by the homeostasis model assessment. Tobacco consumption data were obtained using a standard questionnaire. Results The 4G/4G PAI-1 genotype was significantly associated with a high prevalence of arterial hypertension. This association remained statistically significant even after adjustment for hypertension-related metabolic variables in our population (adjusted odds ratio, 1.858; 95% confidence interval, 1.135–3.018; P = 0.013). Conclusion Our results show that the 4G/4G PAI-1 genotype appears to be associated with an elevated relative risk of developing arterial hypertension, regardless of PAI-1 levels and other hypertension-related factors, in a representative sample of the Spanish population.