Single Nucleotide Polymorphisms in Multiple Novel Thrombospondin Genes May Be Associated With Familial Premature Myocardial Infarction

Topol, Eric J.; McCarthy, Jeanette; Gabriel, Stacey; Moliterno, David J.; Rogers, William J.; Newby, L. Kristin; Freedman, Matt; Metivier, Jennifer; Cannata, Ruth; O’Donnell, Christopher J.; Kottke‐Marchant, Kandice; Murugesan, Gurunathan; Plow, Edward F.; Stenina, Olga I.; Daley, George Q.

doi:10.1161/hc4701.100910

Cited by 260 publications

(232 citation statements)

References 30 publications

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“…Several functions have been attributed to TSP-1 including antiangiogenic [14,38] and proatherogenic [36,40] properties. More recently, this protein has been studied as a potential link between vasculature mechanisms and hyperglycemia [2,39].…”

Section: Discussionmentioning

confidence: 99%

Glucose and insulin modify thrombospondin 1 expression and secretion in primary adipocytes from diet-induced obese rats

et al. 2011

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Thrombospondin 1 (TSP-1), an anti-angiogenic factor and TGF-β activity regulator, has been recently recognized as an adipokine that correlates with obesity, inflammation and insulin-resistance processes. In the present study, epididymal adipocytes of rats that were fed a chow (C) or a high fat diet (HFD) for 50 days, were isolated and incubated (24-72 h) in low (LG; 5.6 mM) or high (HG; 25 mM) glucose, in presence or absence of 1.6 nM insulin. Rats fed the HF diet showed an established obesity state. Serum TSP-1 levels and TSP-1 mRNA basal expression of adipocytes from HFD rats were higher than those from controls. Adipocytes from HFD animals presented an insulin-resistance state, as suggested by the lower insulin-stimulated glucose uptake as compared to controls. TSP-1 expression in culture was higher in adipocytes from obese animals at 24 h, but when the adipocytes were treated with HG, these expression levels dropped dramatically. Later at 72 h, TSP-1 expression was lower in adipocytes from HFD rats, and no effects of the other treatments were observed. Surprisingly, the secretion levels of this protein at 72 h were increased significantly by the HG treatment in both types of adipocytes, although they were even higher in adipocytes from obese animals. Finally, cell viability was significantly reduced by HG treatment in both types of adipocytes. In summary, TSP-1 expression/secretion was modulated in an in vitro model of insulinresistant adipocytes. The difference between expression and secretion patterns suggests a post-transcriptional regulation. The present study confirms that TPS-1 is closely associated with obesity-related mechanisms.

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Section: Discussionmentioning

confidence: 99%

Glucose and insulin modify thrombospondin 1 expression and secretion in primary adipocytes from diet-induced obese rats

et al. 2011

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“…Number of markers than must be genotyped to be 95% confident that the upper bound on stratification is within a particular factor of the best estimate. If we observe a χ 2 value of x and the genome-wide threshold of significance is y, then ruling out stratification as an explanation for the positive association means genotyping enough markers so that the second column in the GeneQuest coronary artery disease study 24 . We randomly selected 83 cases and 80 controls, all European Americans.…”

Section: Figurementioning

confidence: 99%

Assessing the impact of population stratification on genetic association studies

et al. 2004

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Population stratification refers to differences in allele frequencies between cases and controls due to systematic differences in ancestry rather than association of genes with disease. It has been proposed that false positive associations due to stratification can be controlled by genotyping a few dozen unlinked genetic markers. To assess stratification empirically, we analyzed data from 11 case-control and casecohort association studies. We did not detect statistically significant evidence for stratification but did observe that assessments based on a few dozen markers lack power to rule out moderate levels of stratification that could cause false positive associations in studies designed to detect modest genetic risk factors. After increasing the number of markers and samples in a case-cohort study (the design most immune to stratification), we found that stratification was in fact present. Our results suggest that modest amounts of stratification can exist even in well designed studies.

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“…We have sequenced exons and their flanking regions, including the promoter region (1.5 kb), to discover variants in 24 Korean unregulated individual DNA samples using the ABI PRISM 3700 DNA analyzer (Applied Biosystems, Foster City, CA Genotyping with fluorescence polarization detection Twenty polymorphisms of eight candidate genes that might be implicated in clearance of HBV infection and HCC occurrence were genotyped in this study, including -532C＞T, -217G＞A, -6A＞G, and +3889C ＞T in AGT -472insdelA, -285C＞A, +76003A＞C, +84762C＞G, and +86123C＞T in CDH1 (Humar et al, 2002;Nakamura et al, 2002;Wang et al, 2003); -162C＞G, +3552G＞A, and +5789T＞C in COX2 (Fritsche et al, 2001); -2518G＞A and -2076A＞T in MCP1 (Aguilar et al, 2001;Szalai et al, 2001;Kim et al, 2002); +69219G＞T and +91191T＞C in MDR1 (Jamroziak et al, 2004;Kajinami et al, 2004); -403G＞A and -28C＞G in RANTES (Liu et al, 1999); +36412T＞G in THBS2; and +30275G＞ C in THBS4 (Topol et al, 2001;Boekholdt et al, 2002). In addition, three polymorphisms in chemokine receptor 4 (CXCR4) and vimentin (VIM), identified in this study, were also genotyped (Table 2).…”

Section: Sequence Analysis Of the Human Cxcr4 And Vimmentioning

confidence: 99%

Association of common promoter polymorphisms of MCP1 with hepatitis B virus clearance

Park

Kim²,

Cheong³

et al. 2006

Exp Mol Med

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Hepatocellular carcinoma (HCC) is one of the most common malignant cancers closely associated with chronic infection by the hepatitis B virus (HBV) or the hepatitis C virus (HCV) throughout the world. In this study, the genetic associations of 20 known polymorphisms in eight candidate genes, including angiotensinogen (AGT), cadherin 1 (CDH1), cyclooxygenase 2 (COX2), monocyte chemotactic protein-1 (MCP1), multidrug resistance 1 (MDR1), chemokine ligand 5 (RANTES), thrombospondin 2 (THBS2), and thrombospondin 4 (THBS4), were analyzed in a large chronic hepatitis B cohort (n = 1,095) recruited from the Korean population. In addition, three polymorphisms in chemokine receptor 4 (CXCR4) and vimentin (VIM) identified in this study were also genotyped. Using logistic regression analysis controlling possible confounding factors, one common (freq.=0.367) promoter polymorphism of MCP1 (MCP1-2518G>A) among analyzed polymorphisms was significantly associated with clearance of HBV infection. The frequency of homozygotes for the MCP1-2518A allele (MCP1-2518A/A) among chronic hepatitis B virus (HBV) carrier patients was significantly higher than that among spontaneously recovered (SR) subjects (17.7% vs. 10.4%)(OR=1.78, P = 0.004). Our findings imply a plausible explanation for the contribution of host genetic determinants to the variable outcome of HBV infection, which might provide valuable information for future genetic study in this area.

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Single Nucleotide Polymorphisms in Multiple Novel Thrombospondin Genes May Be Associated With Familial Premature Myocardial Infarction

Cited by 260 publications

References 30 publications

Glucose and insulin modify thrombospondin 1 expression and secretion in primary adipocytes from diet-induced obese rats

Glucose and insulin modify thrombospondin 1 expression and secretion in primary adipocytes from diet-induced obese rats

Assessing the impact of population stratification on genetic association studies

Association of common promoter polymorphisms of MCP1 with hepatitis B virus clearance

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