M. Smaoui

Association of SNP3 polymorphism in the apolipoprotein A-V gene with plasma triglyceride level in Tunisian type 2 diabetes.

BackgroundApolipoprotein A-V (Apo A-V) gene has recently been identified as a new apolipoprotein involved in triglyceride metabolism. A single nucleotide polymorphism (SNP3) located in the gene promoter (-1131) was associated with triglyceride variation in healthy subjects. In type 2 diabetes the triglyceride level increased compared to healthy subjects. Hypertriglyceridemia is a risk factor for coronary artery disease. We aimed to examine the interaction between SNP3 and lipid profile and coronary artery disease (CAD) in Tunisian type 2 diabetic patients.ResultsThe genotype frequencies of T/T, T/C and C/C were 0.74, 0.23 and 0.03 respectively in non diabetic subjects, 0.71, 0.25 and 0.04 respectively in type 2 diabetic patients. Triglyceride level was higher in heterozygous genotype (-1131 T/C) of apo A-V (p = 0.024). Heterozygous genotype is more frequent in high triglyceride group (40.9%) than in low triglyceride group (18.8%) ; p = 0.011. Despite the relation between CAD and hypertriglyceridemia the SNP 3 was not associated with CAD.ConclusionIn type 2 diabetic patients SNP3 is associated with triglyceride level, however there was no association between SNP3 and coronary artery disease.

Lipids and lipoprotein(a) concentrations in Tunisian type 2 diabetic patients: Relationship to glycemic control and coronary heart disease

The aim of this study was to evaluate plasma lipoprotein(a) [Lp(a)] concentrations in Tunisian patients with type 2 diabetes mellitus (DM), to correlate the values with other lipid parameters, and to examine the relationship to glycemic control and coronary heart disease (CHD). Diabetic patients with and without CHD (n=200) had significantly higher levels of Lp(a) (327.94+/-239.93 mg/l) and a greater proportion of elevated (>300 mg/l) Lp(a) concentrations (46%) compared with 100 healthy nondiabetic controls (269.83+/-225.6 mg/l, P<.01, and 26%, P<.01), while there were no statistically significant difference between diabetics without CHD (n=100) and controls. No significant association of Lp(a) with glycemic control (HbAlc or fasting blood glucose) was noted in diabetic patients. Positive correlations were observed between Lp(a) levels and total cholesterol and LDL-C in all diabetic patients and particularly in diabetic men. Male patients with CHD showed significantly higher plasma Lp(a) levels than those without CHD (P=.023), and 57.3% of patients with CHD showed increase (>300 mg/l) Lp(a) compared with 33.3% of patients without CHD. Elevated levels of Lp (a) and abnormal lipid profile in diabetic men suggest their involvement in atherogenesis and subsequent development of CHD.

Association between apolipoprotein E polymorphism, lipids, and coronary artery disease in Tunisian type 2 diabetes

BACKGROUND The relationship between apolipoprotein E (ApoE) polymorphism, fasting lipid parameters, and coronary artery disease (CAD) is controversial. METHODS We studied this relationship, for the first time, in Tunisian type 2 diabetic patients. The studied population comprised 157 type 2 diabetic patients (145 of them were not on any lipid-lowering drugs). Fasting lipids were measured by enzymatic methods and ApoE genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS Our results showed that the alleles E2, E3, and E4 were found in 4%, 88%, and 8% of patients, respectively. In the total type 2 diabetic population, no association was found between ApoE polymorphism, lipid parameters, and CAD. However, the E4 allele was associated with elevated low-density lipoprotein cholesterol concentration and with CAD in type 2 diabetic men. CONCLUSION The effect of ApoE polymorphism on CAD is gender-dependent in the Tunisian type 2 diabetic population. ApoE 4 allele may enhance atherogenesis indirectly by a strong effect on low-density lipoprotein cholesterol.

0106: Association of lipoproteina and cholesteryl ester transfer protein-TaqIB polymorphism in Tunisian type 2 diabetes

Lipoprotein (a) [Lp(a)] is a plasma lipoprotein consisting of a LDL-like particle with a molecule of apolipoprotein B100 covalently linked to a very large additional glycoprotein known as apolipoprotein(a). Elevated Lp(a) levels constitute an independent risk factor for cardiovascular disease in the general population. Several studies have examined the possibility that type 2 diabetes could influence Lp(a) concentrations. Cholesteryl ester transfer protein (CETP) plays a key role in lipoprotein metabolism, promoting the exchange of triglycerides (TGs) and cholesteryl esters (CEs) between lipoprotein particles. The CETP TaqIB polymorphism in type 2 diabetes may have an increased risk for coronary artery disease. The aim of the present study was to examine the effect of the genetic polymorphism TaqIB of the CETP on the Lp(a) concentrations and the risk of coronaropathy in a cohort of type 2 diabetes. Plasma Lp(a) levels are not significantly associated with CETP TaqIB polymorphism in type 2 diabetes: no significant difference in the plasma Lp (a) between the diabetics having the genotype B1B1 and those having the genotype B2 (365.8±259 vs. 317±250.1mg; p=0.20). For the diabetics with genotype B1B1, Lp (a) was correlated significantly with the LDL (n=90, r=0.32; p=0.002) and the apoB (n=90, r=0.24, p=0.01). The proportion of the diabetics having the allele B2 and Lp (a) superior to 300mg/l, is clearly more important at those having coronaropathy (51.1 vs. 29.2%; odds ratio=2.53; p=0.03). Lp(a) levels is a risk factor for cardiovascular disease in type 2 diabetic patients. This atherogenic risk seems to depend on the genetic polymorphism TaqIB of the CETP.

Interactions Between Total Plasma Homocysteine, Oxidized LDL Levels, Thiolactonase Activities and Dietary Habits in Tunisian Diabetic Patients

Cardiovascular disease (CVD) is the predominant cause for morbidity and mortality in diabetes mellitus (DM). Patients with diabetes mellitus have two to three times the incidence of atherosclerotic disease compared to the general population (Kannel & McGee, 1979). Several etiologic factors increase susceptibility to CVD in DM including insulin resistance, dyslipidemia, endothelial dysfunction, prothrombosis, and increased protein glycation (Baynes & Thorpe, 1999). Plasma homocysteine levels are elevated in patients with diabetes, particularly in patients with type 2 diabetes as well as in individuals in prediabetic states who exhibit insulin resistance. Homocysteine (Hcy) is a non-essential amino acid that is produced from demethylation of methionine. Hcy can be remethylated into methionine by means of vitamin B12-dependent methionine synthase and 5-methyltetrahydrofolate as a methyl donor. Hcy can be also catabolized into cysteine (the transsulfuration pathway) via cystathionine beta synthase and cystathioninase, both enzymes being vitamin B6dependent. A third way to remove Hcy is conversion to S-adenosylhomocysteine (SAH). The last reaction is mediated by SAH-hydrolase and favors the SAH formation in case of increased Hcy concentrations. S-Adenosyl methionine (SAM) is a universal methyl donor that is formed from methionine and converted into SAH after donating its methyl group. SAH is a potent inhibitor of most known methyltransferases (Kloor & Osswald, 2004). Among the main determinants of tHcy levels in non-diabetic subjects are age, sex, renal function, several diseases, drugs, coffee and chronic alcohol consumption, smoking and physical inactivity (Refsum et al., 2006). Genetic factors and nutritional deficiencies of folate

The effect of apolipoprotein E polymorphism on plasma cholesteryl ester transfer protein activity in type 2 diabetic patients

We studied the relationship between apo E polymorphism and cholesteryl ester transfer protein (CETP) activity in 127 type 2 diabetic patients who did not take lipid lowering drugs. Furthermore, we studied the relationship between apo E and cholesteryl ester transfer protein (CETP) in modulating plasma triglyceride and HDLcholesterol. Apo E genotypes were determined by PCR-RFLP, and CETP activity was measured using an exogenous way. Our results showed that the CETP activity increased significantly in the E2 carrier group compared to E4 carriers and E3/E3 homozygous (84.7 ± 43.9 vs. 62.5 ± 35.9 vs. 52.6 ± 23.6 nmol CE/ml/2h, respectively; p = 0.015). However, there was no association between apo E polymorphism and lipid parameter variations. Even after adjustment for CETP activity, the results remained unchanged, showing that CETP did not step in the relationship between apo E and lipid parameter variations. In conclusion there is an association between apo E polymorphism and CETP activity, and this association did not affect the relationship between apo E polymorphism and triglyceride and HDLcholesterol concentrations.