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

Metabolic syndrome refers to the clustering of disease conditions such as insulin resistance, hyperinsulinemia, dyslipidemia, hypertension, and obesity. To explore the genetic predispositions of this complex syndrome, we conducted a principal components analysis using data on 14 phenotypes related to the risk of developing metabolic syndrome. The subjects were 566 nondiabetic Mexican Americans, distributed in 41 extended families from the San Antonio Family Heart Study. The factor scores obtained from these 14 phenotypes were used in multipoint linkage analysis using SOLAR. Factors were identified that accounted for 73% of the total variance of the original variables: body size-adiposity, insulin-glucose, blood pressure, and lipid levels. Each factor exhibited evidence for either significant or suggestive linkage involving four factor-specific chromosomal regions relating to chromosomes 1, 3, 4, and 6. Significant evidence for linkage of the lipid factor was found on chromosome 4 near marker D4S403 (LOD = 3.52), where the cholecystokinin A receptor (CCKAR) and ADP-ribosyl cyclase 1 (CD38) genes are located. Suggestive evidence for linkage of the body size-adiposity factor to chromosome 1 near marker D1S1597 (LOD = 2.53) in the region containing the nuclear receptor subfamily 0, group B, member 2 gene (NROB2) also was observed. The insulin-glucose and blood pressure factors were linked suggestively to regions on chromosome 3 near marker D3S1595 (LOD = 2.20) and on chromosome 6 near marker D6S 1031 (LOD = 2.08), respectively. In summary, our findings suggest that the factor structures for the risk of metabolic syndrome are influenced by multiple distinct genes across the genome.
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PMID:Principal component for metabolic syndrome risk maps to chromosome 4p in Mexican Americans: the San Antonio Family Heart Study. 1575 39

The cholecystokinin A receptor (CCKAR) is expressed predominantly in the gallbladder and small intestine in the digestive system, where it is responsible for CCK's regulation of gallbladder and small intestinal motility. The effect of CCKAR on small intestinal transit is a physiological response for regulating intestinal cholesterol absorption. The Cckar gene has been identified to be an important gallstone gene, Lith13, in inbred mice by a powerful quantitative trait locus analysis. Knockout of the Cckar gene in mice enhances cholesterol cholelithogenesis by impairing gallbladder contraction and emptying, promoting cholesterol crystallization and crystal growth, and increasing intestinal cholesterol absorption. Clinical and epidemiological studies have demonstrated that several variants in the CCKAR gene are associated with increased prevalence of cholesterol cholelithiasis in humans. Dysfunctional gallbladder emptying in response to exogenously administered CCK-8 is often found in patients with cholesterol gallstones, and patients with pigment gallstones display an intermediate degree of gallbladder motility defect. Gallbladder hypomotility is also revealed in some subjects without gallstones under several conditions: pregnancy, total parenteral nutrition, celiac disease, oral contraceptives and conjugated estrogens, obesity, diabetes, the metabolic syndrome, and administration of CCKAR antagonists. The physical-chemical, genetic, and molecular studies of Lith13 show that dysfunctional CCKAR enhances susceptibility to cholesterol gallstones through two primary mechanisms: impaired gallbladder emptying is a key risk factor for the development of gallbladder hypomotility, biliary sludge (the precursor of gallstones), and microlithiasis, as well as delayed small intestinal transit augments cholesterol absorption as a major source for the hepatic hypersecretion of biliary cholesterol and for the accumulation of excess cholesterol in the gallbladder wall that further worsens impaired gallbladder motor function. If these two defects in the gallbladder and small intestine could be prevented by the potent CCKAR agonists, the risk of developing cholesterol gallstones could be dramatically reduced.
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PMID:An Update on the Lithogenic Mechanisms of Cholecystokinin a Receptor (CCKAR), an Important Gallstone Gene for Lith13. 3326 Mar 32