The important role of APOAV gene variants in determination of plasma triglyceride levels has been shown in many population studies. Recently, an influence of APOAV T-1131>C polymorphism on C-reactive protein (CRP) in young Korean males has been reported. We have therefore analyzed a putative association between T-1131>C, Ser19>Trp and Val153>Met APOAV variants (PCR and restriction analysis) and CRP concentrations in 1119 Caucasian males, aged between 28 and 67 years (49.2±10.8 years). The frequency of C allele carriers was lower in Caucasians than in Koreans (15.5 % vs. 46.2 %). CRP levels did not differ between T/T homozygotes (n=946, 1.61±2.05 mg/l) and carriers of the C allele (n=173, 1.67±1.95 mg/l). Thus, in contrast to Korean males, T-1131>C APOAV variant has no effect on plasma concentrations of CRP in a large group of Caucasian males. Other APOAV variants (Ser19>Trp and Val153>Met) did not also influence plasma concentrations of CRP. APOAV variants are unlikely to be an important genetic determinant of plasma CRP concentrations in Caucasian males.
Coronary artery bypass graft (CABG) surgery is one of the most commonly performed operations worldwide. We compared genotype frequencies of three major cardiovascular disease (CVD)-associated genetic markers (ANRIL, FTO and 2q36.3 locus) between 753 patients who underwent CABG at the Institute for Clinical and Experimental Medicine (Prague, Czech Republic) and 2,559 controls from the Czech post-MONICA study. Subjects with at least one major A allele in the rs10757274 polymorphism (ANRIL) were more prevalent in patients after CABG than in the controls (81.7 % vs 72.7 %; OR [95 % CI] 1.67 [1.35-2.05]; P < 0.0001). In contrast, variants within the FTO gene (OR 0.87; 95% CI, 0.70-1. 09 in a TT vs. GG comparison, P = 0.24) and 2q36.3 locus (OR 1.16; 95% CI, 0.98-1.37 in a +A vs. CC comparison, P = 0.08) were not significantly associated with CVD in our study. Variants were not associated with anthropometric, biochemical, or clinical characteristics within the patient group. Our study suggests that patients with CABG are more commonly carriers of some but not all CVD-associated alleles.
Animal studies (on transgenic and knock-out mice) and human association analysis assessed the importance of APOAV gene for plasma triglyceride determination. New APOAV missense variants (Val153 → Met and Cys185 → Gly) have been detected recently. We have analyzed these variants in 83 unrelated patients with extreme lipid parameters (triglycerides of 20.4±12.8 mmol/l and total cholesterol of 10.4±3.7 mmol/l) and in a control population group consisting of 2,559 unrelated Caucasians. In patients, the frequency of the Met153 carriers was slightly but not significantly higher (9.64 % vs. 6.49 %) compared to the population sample. This suggested that Val153 → Met polymorphism in the APOAV gene does not represent an important risk factor for developing the extreme levels of plasma triglycerides. We did not detect carriers of the Gly185 allele among patients or 420 healthy individuals. We suppose that this variant is probably not present in Caucasian populations.
Through the analysis of the common apolipoprotein (apo) E gene polymorphism in large Caucasian population study with the PCR and subsequent restriction analysis, we have identified carriers of mutant allele Arg136→Ser. Both of them (71-years-old female and her 43-years-old son) have normal lipid parameters. We suggest that Arg136→Ser mutation in apoE is not necessarily connected with elevated lipid levels in all cases. Furthermore, so far unidentified factors (environmental and/or genetic) are important for the development of lipid metabolism disorders in apoE Arg136→Ser mutation carriers.
The role of the FTO gene in obesity development is well established in populations around the world. The NYD-SP18 variant has been suggested to have a similar effect on BMI, but the role of this gene in determining BMI has not yet been verified. The objective of ou r study was to confirm the association between NYD-SP18 rs6971091 SNP and BMI in the Slavic population and to analyze i) the gender-specific effects of NYD-SP18 on BMI and ii) the si multaneous effect of FTO rs17817449 and NYD-SP18 on BMI. We analyzed a sample of a large adult population based on the post-MONICA study (1,191 males and 1,368 females). Individuals were analyzed three times over 9 years. NYD-SP18 rs6971091 SNP is related to BMI in males (2000/1 GG 28.3±3.7 kg/m 2 vs. +A 27.5±3.7 kg/m 2 P<0.0005; in other examinations P<0.05 and <0.005), but not in females (all P values over 0.48 in all three examinations). Further analysis revealed the significant additive effect (but not the interaction) of FTO and NYD-SP18 SNPs on BMI in males (all P<0.01). These results suggest that association between NYD-SP18 rs6971091 SNP and BMI may be restricted to males. Furthermore, variants within NYD-SP18 and FTO genes revealed a significant additive effect on BMI values in males., J. A. Hubacek, D. Dlouha, V. Lanska, V. Adamkova., and Obsahuje bibliografii
The treatment of hypercholesterolemia with bile acid (BA)
sequestrants results in upregulation of BA synthesis through the
classical pathway initiated by cholesterol 7α-hydroxylase (CYP7A1). To characterize the detailed dynamics of serum lipid and BA concentrations and the BA synthesis rate in response to treatment with BA sequestrants and to determine whether the -203A/C promoter polymorphism of the CYP7A1 encoding gene (CYP7A1) affects such a response, this pilot study was carried out in healthy men (8
h omozygous for the -203A allele and 8 homozygous for the -203C allele of CYP7A1). The subjects were treated for 28 days with colesevelam
and blood was drawn for analysis before and on days 1, 3, 7, 14 and 28 of treatment. The response of lipids, BA, fibroblast growth factor-19 (FGF19) and 7α-hydroxy-4-cholesten-3-one (C4) to colesevelam did not differ between carriers of -203A and -203C alleles; their data were then aggregated for further analysis. Colesevelam treatment caused immediate suppression of FGF19 concentration and a fivefold increase in CYP7A1 activity, as assessed from C4 concentration, followed by a 17% decrease in LDL-cholesterol. Although total plasma BA concentrations were not affected, the ratio of cholic acid/total BA rose from 0.25±0.10 to 0.44±0.16 during treatment at the expense of decreases in chenodeoxycholic and deoxycholic acid.