Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Familial combined hyperlipidemia (FCHL, MIM-144250) is a common, multifactorial and heterogeneous dyslipidemia predisposing to premature coronary artery disease and characterized by elevated plasma triglycerides, cholesterol, or both. We identified a mutant mouse strain, HcB-19/Dem (HcB-19), that shares features with FCHL, including hypertriglyceridemia, hypercholesterolemia, elevated plasma apolipoprotein B and increased secretion of triglyceride-rich lipoproteins. The hyperlipidemia results from spontaneous mutation at a locus, Hyplip1, on distal mouse chromosome 3 in a region syntenic with a 1q21-q23 FCHL locus identified in Finnish, German, Chinese and US families. We fine-mapped Hyplip1 to roughly 160 kb, constructed a BAC contig and sequenced overlapping BACs to identify 13 candidate genes. We found substantially decreased mRNA expression for thioredoxin interacting protein (Txnip). Sequencing of the critical region revealed a Txnip nonsense mutation in HcB-19 that is absent in its normolipidemic parental strains. Txnip encodes a cytoplasmic protein that binds and inhibits thioredoxin, a major regulator of cellular redox state. The mutant mice have decreased CO2 production but increased ketone body synthesis, suggesting that altered redox status down-regulates the citric-acid cycle, sparing fatty acids for triglyceride and ketone body production. These results reveal a new pathway of potential clinical significance that contributes to plasma lipid metabolism.
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PMID:Positional cloning of the combined hyperlipidemia gene Hyplip1. 1175 87

The upstream stimulatory factor 1 (USF1) gene has been shown to play an essential role as the cause of familial combined hyperlipidemia, and there are several association studies on the relationship between USF1 and metabolic disorders. In this study, we analyzed two single nucleotide polymorphisms in USF1 rs2073653 (306A>G) and rs2516840 (1748C>T) between the case (dyslipidemia or obesity) group and the control group in premenopausal females, postmenopausal females, and males among 275 Korean subjects. We observed a statistically significant difference in the GC haplotype between body mass index (BMI) > or =25 kg/m2) and BMI <25 kg/m2 groups in premenopausal females ( chi2=4.23, p=0.04). It seems that the USF1 GC haplotype is associated with BMI in premenopausal Korean females.
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PMID:Body mass index is associated with USF1 haplotype in Korean premenopausal women. 1830 4

USF1 (upstream stimulatory factor 1) is a transcription factor associated with familial combined hyperlipidemia and coronary artery disease in humans. However, whether USF1 is beneficial or detrimental to cardiometabolic health has not been addressed. By inactivating USF1 in mice, we demonstrate protection against diet-induced dyslipidemia, obesity, insulin resistance, hepatic steatosis, and atherosclerosis. The favorable plasma lipid profile, including increased high-density lipoprotein cholesterol and decreased triglycerides, was coupled with increased energy expenditure due to activation of brown adipose tissue (BAT). Usf1 inactivation directs triglycerides from the circulation to BAT for combustion via a lipoprotein lipase-dependent mechanism, thus enhancing plasma triglyceride clearance. Mice lacking Usf1 displayed increased BAT-facilitated, diet-induced thermogenesis with up-regulation of mitochondrial respiratory chain complexes, as well as increased BAT activity even at thermoneutrality and after BAT sympathectomy. A direct effect of USF1 on BAT activation was demonstrated by an amplified adrenergic response in brown adipocytes after Usf1 silencing, and by augmented norepinephrine-induced thermogenesis in mice lacking Usf1. In humans, individuals carrying SNP (single-nucleotide polymorphism) alleles that reduced USF1 mRNA expression also displayed a beneficial cardiometabolic profile, featuring improved insulin sensitivity, a favorable lipid profile, and reduced atherosclerosis. Our findings identify a new molecular link between lipid metabolism and energy expenditure, and point to the potential of USF1 as a therapeutic target for cardiometabolic disease.
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PMID:USF1 deficiency activates brown adipose tissue and improves cardiometabolic health. 2681 96

Serum lipid profile which is determined by genotype-phenotype relationship plays a significant role in the development of cardiovascular disease. Upstream stimulatory factor 1 (USF1), has been reported to be associated with serum lipid levels in different population, hence, this study investigated the association of variants in USF1 with serum lipid profile in adults in Lagos state, Nigeria. We genotyped rs3737787 (11235C > T) and rs550376620 (10488G>A) with PCR-RFLP in 384 participants and we used logistic regression to assess the association of these variants with serum lipid levels. The minor allele frequency observed in 10488G>A in both case and control groups was 5% while the minor allele of 11235C > T was observed to be more frequent in the control when compared to the dyslipidemic subjects (24% vs 12%; p =1.84e-05). Levels of total cholesterol, triglycerides, and LDL-c in dyslipidemic subjects with CC genotype of 11235C > T were significantly higher compared to CT and TT genotypes (p < 0.001; p < 0.0001 and p< 0.0001 respectively). Logistic regression with adjustment for age, gender and BMI, showed that the minor allele carriers of 11235C > T have a reduced risk of dyslipidemia (Odds ratio: 0. .043, 95% confidence interval (CI): (0.006 - 0.331, p = 0.002). Our findings revealed that rs3737787 is associated with lipid phenotype in Nigerian population.
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PMID:Polymorphism rs3737787 of Upstream Stimulatory Factor 1 Gene is Associated with Serum Lipid Phenotype in Nigerian Population. 3330 80