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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Macrovascular disease is a major complication of type 2 diabetes. Epidemiological data suggest that the risk of macrovascular complications may predate the onset of hyperglycemia. Hypertriglyceridemia, low levels of HDL cholesterol, and an atherogenic profile characterize the insulin resistance/metabolic syndrome that is also prevalent among nondiabetic members of familial type 2 diabetic kindreds. To identify the genes for lipid-related traits, we first performed a 10-cM genome scan using 440 markers in 379 members of 19 multiplex families ascertained for two diabetic siblings (screening study). We then extended findings for three regions with initial logarithm of odds (LOD) scores >1.5 to an additional 23 families, for a total of 576 genotyped individuals (extended study). We found heritabilities for all lipid measures in the range of 0.31 to 0.52, similar to those reported by others in unselected families. However, we found the strongest evidence for linkage of triglyceride levels to chromosome 19q13.2, very close to the ApoC2/ApoE/ApoC1/ApoC4 gene cluster (LOD 2.56) in the screening study; the LOD increased to 3.16 in the extended study. Triglyceride-to-HDL cholesterol ratios showed slightly lower LOD scores (2.73, extended family) in this same location. Other regions with LOD scores >2.0 included HDL linkage to chromosome 1q21-q23, where susceptibility loci for both familial type 2 diabetes and familial combined hyperlipidemia have been mapped, and to chromosome 2q in the region of the NIDDM1 locus. Neither region showed stronger evidence for linkage in the extended studies, however. Our results suggest that genes in or near the ApoE/ApoC2/ApoC1/ApoC4 cluster on 19q13.2 may contribute to the commonly observed hypertriglyceridemia and low HDL seen in diabetic family members and their offspring, and thus may be a candidate locus for the insulin resistance syndrome.
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PMID:Quantitative trait linkage analysis of lipid-related traits in familial type 2 diabetes: evidence for linkage of triglyceride levels to chromosome 19q. 1181 65

Evidence for a genetic basis for type 2 diabetes and the metabolic syndrome has been derived from studies of families, twins and populations with genetic admixture. Identification of genes associated with disease pathogenesis is now underway using techniques such as genome scanning by positional cloning and the candidate gene approach. Genome scanning in several different ethnic groups has identified chromosome regions harbouring type 2 diabetes susceptibility genes such as the novel gene, calpain 10 (CAPN10). The hepatic nuclear factor 4alpha (HNF4alpha) gene partly explains the linkage peak on chromosome 20, while the upstream transcription factor (USF1) is associated with familial combined hyperlipidaemia (FCHL) and maps close to the type 2 diabetes associated 1q peak. Peroxisome proliferator-activated receptor gamma (PPARgamma) was identified as a candidate gene based on its biology. A Pro12Ala variant of this gene has been associated with an increased risk of type 2 diabetes. Many genes accounting for monogenic forms of diabetes have been identified--such as maturity onset diabetes of the young (MODY); glucokinase (GCK) and HNF1alpha mutations being the most common causes of MODY. GCK variants result in 'mild' diabetes or impaired glucose tolerance (IGT) and relatively few cardiovascular complications, while HNF1alpha-associated MODY is more typical of type 2 diabetes, frequently being treated with sulphonylureas or insulin and resulting in microvascular complications. Testing for single gene disorders associated with type 2 diabetes and obesity may determine cause, prognosis and appropriate treatment; however, for the more common polygenic diseases this is not the case. In type 2 diabetes, molecular genetics has the potential to enhance understanding of disease pathogenesis, and help formulate preventative and treatment strategies.
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PMID:Searching for genes in diabetes and the metabolic syndrome. 1603 91

Patients with metabolic syndrome are at increased risk of developing cardiovascular disease. The combinations of the haplotype created by the alleles of three single nucleotide polymorphisms (SNPs): SNP-43, -19, and -63 of the Calpain-10 gene (CAPN10), have been reported to be associated with the risk of type 2 diabetes in many populations. The aim of this study was to examine the association of the CAPN10 polymorphism with metabolic syndrome in patients with type 2 diabetes in Korea. Overall, 382 patients with type 2 diabetes were enrolled in this study. All the subjects were genotyped according to CAPN10 SNP-43, -19, and -63. The restriction fragment length polymorphism method was used for the three SNPs. The baseline presence of components of metabolic syndrome was determined. Two hundred and sixty-five (69.4%) patients had metabolic syndrome. Patients with the 111/121 haplotype combination showed a higher risk of hypertension than the other haplotype combinations (odd ratio (OR)=2.334, P=0.010). Patients with the 111/121 haplotype combination had a significantly high risk of metabolic syndrome (OR=1.927, P=0.042). The results of this study suggest that a novel 111/121 haplotype combination created by the CAPN10 SNP-43, -19, and -63 increases the susceptibility to the metabolic syndrome in patients with type 2 diabetes.
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PMID:Haplotype combination of Calpain-10 gene polymorphism is associated with metabolic syndrome in type 2 diabetes. 1654 86

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.
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PMID:The CAPN10 gene is associated with insulin resistance phenotypes in the Spanish population. 1869 25

Both insulin resistance and dyslipidaemia are determined by genetic and environmental factors. Depending on their expression and their function, gene variants may influence either insulin action or other metabolic traits. Nutrition also plays an important role in the development and progression of these conditions. Genetic background may interact with habitual dietary fat composition, affecting predisposition to insulin resistance syndrome and individual responsiveness to changes in dietary fat intake. In this context, nutrigenetics has emerged as a multidisciplinary field focusing on studying the interactions between nutritional and genetic factors and health outcomes. Due to the complex nature of gene-environment interactions, however, dietary therapy may require a "personalized" nutrition approach in the future. Although the results have not always been consistent, gene variants that affect primary insulin action, and particularly their interaction with the environment, are important modulators of glucose metabolism. The purpose of this review is to present some evidence of studies that have already demonstrated the significance of gene-nutrient interactions (adiponectin gene, Calpain-10, glucokinase regulatory protein, transcription factor 7-like 2, leptin receptor, scavenger receptor class B type I etc.) that influence insulin resistance in subjects with metabolic syndrome.
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PMID:Metabolic syndrome: evidences for a personalized nutrition. 2209 24