Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Analysis of variants in three genes encoding oxysterol-binding protein (OSBP) homologues (OSBPL2, OSBPL9, OSBPL10) in Finnish families with familial low high-density lipoprotein (HDL) levels (N = 426) or familial combined hyperlipidemia (N = 684) revealed suggestive linkage of OSBPL10 single-nucleotide polymorphisms (SNPs) with extreme end high triglyceride (TG; >90th percentile) trait. Prompted by this initial finding, we carried out association analysis in a metabolic syndrome subcohort (Genmets) of Health2000 examination survey (N = 2,138), revealing association of multiple OSBPL10 SNPs with high serum TG levels (>95th percentile). To investigate whether OSBPL10 could be the gene underlying the observed linkage and association, we carried out functional experiments in the human hepatoma cell line Huh7. Silencing of OSBPL10 increased the incorporation of [(3)H]acetate into cholesterol and both [(3)H]acetate and [(3)H]oleate into triglycerides and enhanced the accumulation of secreted apolipoprotein B100 in growth medium, suggesting that the encoded protein ORP10 suppresses hepatic lipogenesis and very-low-density lipoprotein production. ORP10 was shown to associate dynamically with microtubules, consistent with its involvement in intracellular transport or organelle positioning. The data introduces OSBPL10 as a gene whose variation may contribute to high triglyceride levels in dyslipidemic Finnish subjects and provides evidence for ORP10 as a regulator of cellular lipid metabolism.
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PMID:OSBPL10, a novel candidate gene for high triglyceride trait in dyslipidemic Finnish subjects, regulates cellular lipid metabolism. 1955 2

The oxysterol hypothesis of cholesterol homeostasis states that oxysterol mediates feedback regulation of cholesterol biosynthesis. Oxysterol-binding proteins have been implicated in the control of lipid synthesis and metabolism. In a genome-wide case-control association study in Japanese individuals, we found that the three single-nucleotide polymorphisms (SNPs) with the smallest P-values were located in the fifth intronic region of the oxysterol-binding protein-like 10 (OSBPL10) gene. In this study, we examined the association between polymorphisms in the OSBPL10 gene and risk factors for the metabolic syndrome in the Tanno and Sobetsu Study. We selected four SNPs, including three non-coding SNPs in intron 5 and a coding SNP (D254N) in exon 6. Genotype frequencies of the polymorphisms satisfied the conditions for Hardy-Weinberg equilibrium. We found that the low-density lipoprotein (LDL) cholesterol of individuals with the rs2290532 (D254N) polymorphism was significantly greater in subjects with the CC+CT genotype than in subjects with the TT genotype (124.3+/-1.3 vs. 111.6+/-4.1 mg per 100 ml, P=0.009). However, there were no significant differences in systolic or diastolic blood pressure, high-density lipoprotein cholesterol or triglyceride levels. Multiple regression analysis showed that rs2290532 (D254N) was associated with LDL cholesterol independent of age, sex or body mass index. Comparison of the genotype frequency in both groups indicated that the genotype associated with low risk (TT) reduced the risk of hyper-LDL cholesterolemia significantly (P=0.003), with an odds ratio of 0.35 (95% confidence interval=0.17-0.76). Overall, the rs2290532 (D254N) polymorphism in OSBPL10 may predispose individuals with this SNP to hyper-LDL cholesterolemia.
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PMID:Variation in OSBPL10 is associated with dyslipidemia. 2022 71