Expression of inflammatory molecules and associations with BMI in children.

BACKGROUND: Adipose tissue secrets several adipokines that have been proposed to be enrolled in many inflammatory pathways. Our aim was to investigate the adipokine expression in adipose tissue and peripheral blood mononuclear cells (PBMCs) in children. MATERIALS AND METHODS: Thirty-one (17 males and 14 females) healthy children aged 10.9 +/- 1.8 years with a body mass index (BMI) of 19.3 +/- 3.5 kg m(-2) were enrolled. Adipokines (TNF-alpha, IL-6 and leptin) gene expression was quantified by real-time quantitative PCR in adipose tissue and PBMCs from the same children. Their serum levels were also measured. RESULTS: BMI was positively correlated with leptin gene expression in adipose tissue and with leptin serum levels (beta = 0.476, P = 0.006 and beta = 0.576, P = 0.003 respectively). Leptin's serum levels were positively correlated with leptin gene expression in adipose tissue (beta = 0.462, P = 0.02). Adipose tissue gene expression of leptin and TNF-alpha and serum leptin and TNF-alpha serum levels were positively correlated (beta = 0.752, P < 0.001, beta = 0.311 and P = 0.015 respectively). In PBMCs, a positive correlation between TNF-alpha and IL-6 expression was found (beta = 0.526, P = 0.042). CONCLUSION: We demonstrated powerful correlations of adipokines gene expression in adipose tissue and PBMCs in children, underlying that these molecules share common pathways related to childhood obesity.

Twenty-four novel mutations identified in a cohort of 85 patients by direct sequencing of the SLC3A1 and SLC7A9 cystinuria genes.

Mutations in the SLC3A1 and SLC7A9 genes cause cystinuria (OMIM 220100), an autosomal recessive disorder of amino acid transport and reabsorption in the proximal renal tubule and in the epithelial cells of the gastrointestinal tract. In an attempt to characterize the molecular defect in the SLC3A1 and SLC7A9 genes, we analyzed a cohort of 85 unrelated subjects clinically diagnosed as affected by cystinuria on the basis of stone formation, prevalently of Italian and Greek origin. Analysis of all coding region and exon-intron junctions of the SLC3A1 and SLC7A9 genes by using direct sequencing method allowed us to identify 62 different mutations in 83 out of 85 patients accounting for 90.5% of all affected chromosomes. Twenty-four out of 62 are novel mutations, 9 in SLC3A1 and 15 in SLC7A9. In conclusion, this report expands the spectrum of SLC3A1 and SLC7A9 mutations and confirms the heterogeneity of this disorder.

Chios mastic treatment of patients with active Crohn's disease.

AIM: To evaluate the effectiveness of mastic administration on the clinical course and plasma inflammatory mediators of patients with active Crohn's disease (CD). METHODS: This pilot study was conducted in patients with established mild to moderately active CD, attending the outpatient clinics of the hospital, and in healthy controls. Ten patients and 8 controls were recruited for a 4-wk treatment with mastic caps (6 caps/d, 0.37 g/cap). All patients successfully completed the protocol. CD Activity Index (CDAI), Nutritional Risk Index (NRI), C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), and total antioxidant potential (TAP) were evaluated in the plasma at baseline and at the end of the treatment period. Results were expressed as mean values +/- SE and P < 0.05 was considered to indicate statistical significance. RESULTS: Patients exhibited significant reduction of CDAI (222.9 +/- 18.7 vs 136.3 +/- 12.3, P = 0.05) as compared to pretreament values. Plasma IL-6 was significantly decreased (21.2 +/- 9.3 pg/mL vs 7.2 +/- 2.8 pg/ mL, P = 0.027), and so did CRP (40.3 +/- 13.1 mg/mL vs 19.7 +/- 5.5, P = 0.028). TAP was significantly increased (0.15 +/- 0.09 vs 0.57 +/- 0.15 mmol/L uric acid, P = 0.036). No patient or control exhibited any kind of side effects. CONCLUSION: The results suggest that mastic significantly decreased the activity index and the plasma levels of IL-6 and CRP in patients with mildly to moderately active CD. Further double-blind, placebo-controlled studies in a larger number of patients are required to clarify the role of this natural product in the treatment of patients with CD.

The Pro12Ala polymorphism in PPARgamma2 gene affects lipid parameters in Greek primary school children: A case of gene-to-gender interaction.

BACKGROUND: In the present study we sought to evaluate the impact of the PPAR-gamma2 Pro12Ala polymorphism on blood lipid levels of primary school children. METHODS: 81 male and 92 female schoolchildren were genotyped. Biochemical, anthropometric, and lifestyle variables were assessed. RESULTS: 14.1% females and 14.8% males were heterozygotes, while the rest of the subjects were homozygotes for the Pro allele. A significant interaction between the PPARgamma-2 gene and gender on blood lipid levels was detected. In particular, Pro/Pro females exhibited higher values of total cholesterol (194 +/- 32 vs 180 +/- 28 mg/dL, P = 0.06) and triglycerides (94 +/- 31 vs 77 +/- 11 mg/dL, P = 0.045) compared to Pro/Ala individuals. The gene-to-gender interaction term was highly significant (P < 0.001). On the other hand, Pro/Pro males showed higher values of HDL cholesterol (47 +/- 8 vs 43 +/- 9 mg/dL, P = 0.001), lower total cholesterol/HDL ratio (4.04 +/- 0.59 vs 4.45 +/- 0.61, P = 0.031), lower values of apoB (59.8 +/- 11.3 vs 66.8 +/- 6.6 mg/dL, P = 0.007) and lower values of apoB/apoA1 ratio (0.41 +/- 0.09 vs 0.48 +/- 0.08, P = 0.019) compared with Pro/Ala. Even after adjusting for body mass index (BMI), total energy intake, total fat intake and saturated fat intake, differences in total cholesterol/high-density lipoprotein (HDL) cholesterol and the apoB/apoA1 ratios remained significant. Regarding females, no differences were observed among genotypes concerning total cholesterol/HDL levels (P for gene-to-gender interaction = 0.001) and the apoB/apoA1 levels (P for gene-to-gender interaction = 0.029). CONCLUSION: We show for the first time a gene-to-gender interaction on total cholesterol/HDL and apoB/apoA1 ratios, in male schoolchildren genotyped for PPAR-gamma2 Pro12Ala.

Different genes and polymorphisms affecting high-density lipoprotein cholesterol levels in Greek familial hypercholesterolemia patients.

Familial Hypercholesterolemia (FH) is a genetic disorder characterized by high low-density lipoprotein cholesterol (LDL-C) concentrations that frequently gives rise to premature coronary artery disease. The clinical expression of FH is highly variable, even in patients carrying the same LDL receptor gene mutation. This variability may be due to environmental and other genetic factors. We investigated the effect of APOCIII T1100C, FV Gln506Arg, ADRB2 Glu27Gln, SELE Ser128Arg, SELE Leu554Phe, and ENaCa Ala663Thr polymorphisms on the HDL-C variations in 84 patients with FH. For ApoCIII T1100C, subjects with the TT genotype presented higher HDL-C levels than the other genotype groups (p = 0.046). Similarly the presence of the Gln allele in ADRB2 27 Glu/Gln heterozygotes and ADRB2 27 Gln/Gln homozygotes was associated with higher HDL-C levels (p = 0.014). Among the other polymorphisms tested, none of them were associated with variations in HDL-C levels. The influence of each polymorphism on lipid concentrations was evaluated with linear regression analyses after adjustment for age and sex. Among the variables studied including total cholesterol, LDL-C, high-density lipoprotein (HDL)-C, triglycerides, apolipoprotein A (Apo-A) and B (Apo-B), and lipoprotein alpha (LP alpha), HDL-C concentration was significantly different in models applied for polymorphisms ApoCIII T1100C, FV Gln506Arg, and ADRB2 Glu27Gln (p = 0.01, p = 0.018, p = 0.04, respectively). These results suggest that HDL-C levels in FH heterozygotes may be affected by several different genetic variants.

Management of a patient with a null low-density lipoprotein receptor mutation: a case report.

A 13-year-old Greek boy with severe dyslipidemia, large tuberous xanthomas over the knees and elbows, Achilles' tendon xanthomas, and a bilateral corneal arcus was referred to the Lipid Clinic. He had a supravalvular aortic stenosis, 50% to 60% stenosis of both carotid arteries, and normal coronary arteries. Familial hypercholesterolemia was clinically diagnosed. A V408M null low-density lipoprotein receptor (LDLR) mutation was identified in homozygosity. He responded to lipid-lowering drugs by decreasing total cholesterol by 32%, low-density lipoprotein cholesterol by 33%, and triglyceride levels by 30%. Additional treatment with low-density lipoprotein-apheresis further decreased total cholesterol by 52%, low-density lipoprotein cholesterol by 55%, and triglycerides by 43%. Low-density lipoprotein cholesterol levels between apheresis sessions showed a declining pattern. A significant regression of tuberous xanthomas was noted. A suitable combination of lipid-lowering drugs is effective even in this case of homozygosity for a null LDLR mutation. Furthermore, the coadministration of statins, cholestyramine, and ezetimibe during low-density lipoprotein-apheresis tends to counterbalance the postapheresis relapse in low-density lipoprotein cholesterol levels.

The effect of minimal dietary changes with raisins in NAFLD patients with non-significant fibrosis: a randomized controlled intervention.

Aiming at investigating the potential effect of minimal dietary changes in NAFLD patients with non-significant fibrosis, 55 patients with NAFLD were enrolled in a randomized controlled clinical trial. Patients were assigned into two isocaloric dietary treatment groups for 24 weeks: (a) nutritional counseling (Control arm, N = 27), (b) nutritional counseling with currants included (two fruit servings, 36 g per day), substituting snacks of similar caloric content (Currant arm, N = 28). Clinical tests, anthropometrics, inflammatory and oxidative stress markers were conducted pre- and post-intervention. A total of 50 patients completed the trial. Significant differences between the two arms post-intervention were observed in fasting glucose and in IL-6 levels, these being significantly decreased only in Currant patients. Body weight, BMI, HbA1c, CRP and EUS values decreased in both arms, differences being insignificant between the two arms post-intervention. Participants in the Currant arm had significantly reduced total body fat, WC and trunk fat. Ultrasound scanning improved significantly in patients snacking currants daily. Also, volunteers enrolled in the Currant arm showed a reduced intake of saturated fatty acids. Because BW regulation has been officially recognised as a treatment approach in NAFLD an additional analysis was repeated in patients adhering to this. Post-intervention, the decrease in IL-6 and in fasting glucose was significantly higher in Currant patients who lost BW compared to their counterparts in the Control arm. Conclusively, minimal modifications in snacking choices, such as the inclusion of dried grapes in diet, are beneficial in NAFLD patients with non-significant fibrosis.

An association between the methylenetetrahydrofolate reductase (MTHFR) C677T mutation and inflammation markers related to cardiovascular disease.

BACKGROUND: Prospective studies have identified many markers of systemic inflammation that are powerful predictors of future cardiovascular events. The methylenetetrahydrofolate reductase (MTHFR) C677T genotype, a common polymorphism that induces hyperhomocysteinaemia, has been proposed as a genetic risk factor for cardiovascular disease. In this work, we evaluated the relationship between the levels of inflammation markers and MTHFR genotype among cardiovascular disease free subjects of the ATTICA study. METHODS: During 2001-2002, we randomly enrolled for genetic evaluation 574 subjects from Attica region, Greece. In this work, we investigated demographic, lifestyle, clinical, biochemical and genetic information from 322 men (46+/-13 years) and 252 women (45+/-14 years). Among other characteristics, we measured various inflammatory markers levels in relation to C677T MTHFR genotype distribution. RESULTS: The MTHFR genotypes distribution was: homozygous normal (CC) genotype, 41%; heterozygous (CT), 48%; and homozygous mutant (TT) genotype, 11%. C-reactive protein (CRA), fibrinogen, white blood cell (WBC) counts and amyloid-a levels were higher in TT compared to CC and CT genotypes (p<0.01), in both genders, even after controlling for various potential confounders. CONCLUSION: The observed association between markers of systemic inflammation with MTHFR genotype may state a hypothesis for a common pathobiological mechanism between inflammation process and MTHFR, which is a key enzyme in homocysteine (Hcy) metabolism.

LDL-receptor mutations in Europe.

Familial hypercholesterolemia (FH) is a clinical definition for a remarkable increase of cholesterol serum concentration, presence of xanthomas, and an autosomal dominant trait of either increased serum cholesterol or premature coronary artery disease (CAD). The identification of the low-density lipoprotein (LDL)-receptor (LDLR) as the underlying cause and its genetic characterization in FH patients revealed more insights in the trafficking of LDL, which primarily transports cholesterol to hepatic and peripheral cells. Mutations within LDLR result in hypercholesterolemia and, subsequently, cholesterol deposition in humans to a variable degree. This confirms the pathogenetic role of LDLR and also highlights the existence of additional factors in determining the phenotype. Autosomal dominant FH is caused by LDLR deficiency and defective apolipoprotein B-100 (APOB), respectively. Heterozygosity of the LDLR is relatively common (1:500). Clinical diagnosis is highly important and genetic diagnosis may be helpful, since treatment is usually effective for this otherwise fatal disease. Very recently, mutations in PCSK9 have been also shown to cause autosomal dominant hypercholesterolemia. For autosomal recessive hypercholesterolemia, mutations within the so-called ARH gene encoding a cellular adaptor protein required for LDL transport have been identified. These insights emphasize the crucial importance of LDL metabolism intra- and extracellularly in determining LDL-cholesterol serum concentration. Herein, we focus on the published European LDLR mutation data that reflect its heterogeneity and phenotypic penetrance.

Molecular characterization of familial hypercholesterolemia in German and Greek patients.

We used the denaturing gradient gel electrophoresis (DGGE) method to define mutations in the promoter region, the 18 exons, and their flanking intronic sequences of the low-density lipoprotein (LDL) receptor gene LDLR, causing familial hypercholesterolemia (FH) phenotype in 100 German and in 100 Greek hypercholesterolemic individuals. In addition, we tested all patients for the presence of mutations in codons 3456-3553 of the gene encoding apolipoprotein B-100 (APOB). Twenty-six aberrant DGGE patterns were identified and subsequently directly sequenced. In LDLR, two novel missense mutations (c.1957G>T/p.V653F, c.647 G>A/p.C216Y) and one novel homozygous base substitution c.1-156 C>T in the repeat 2 of the promoter region were identified among German FH patients; one novel splice site c.1060+10C>G was identified among Greek FH patients. One of the German FH patients was a carrier for the mutations c.1171G>A/p.A391T and p.V653F, and two of the Greek FH patients were compound heterozygotes for the mutations c.1150C>T/p.Q384X and c.1158C>G/p.D386E. Two German FH patients carried the mutation p.R3500Q within APOB. Comparing the mutations within the LDLR gene of the two European FH populations, the German population seems to be more heterogeneous than the Greek cohort. Further studies in progress are trying to elucidate the responsiveness to drug therapy in association with LDLR genotype and the nutritional habits of the two FH populations.

Antiatherogenic effect of Pistacia lentiscus via GSH restoration and downregulation of CD36 mRNA expression.

Pistacia lentiscus var. Chia (Anacardiaceae) grows almost exclusively on Chios Island, Greece, and gives a resinous exudate resin used for culinary purposes by Mediterranean people. We investigated the molecular mechanisms through which total polar extract of the resin inhibits oxidized low-density lipoprotein (oxLDL) cytotoxic effect on peripheral blood mononuclear cell (PBMC). Cells exposed to oxLDL underwent apoptosis and necrosis, dependent on the duration of exposure. When culturing cells with oxLDL and the polar extract concurrently, we observed inhibition of both the phenomena. Because under oxidative stress the pro-oxidant systems outbalance the antioxidant, potentially producing oxidative damage and ultimately leading to cell death, we measured the levels of intracellular antioxidant glutathione (GSH). Additionally, we measured CD36 expression, a class B scavenger receptor, on CD14-positive cells, as CD36 has been identified as the oxLDL receptor in macrophages and may play a pivotal role in atherosclerotic foam cell formation. oxLDL decreased GSH levels and upregulated CD36 expression. P. lentiscus extract restored GSH levels and downregulated CD36 expression, even at the mRNA level. In order to find out the biologically drastic constituents of the resin's polar extract, fractions derived from RP-HPLC analysis were examined for their antioxidant effect on oxidatively stressed PBMC. The triterpenoid fraction revealed remarkable increase in intracellular GSH. We suggest GSH restoration and downregulation of CD36 mRNA expression as the pathways via which P. lentiscus triterpenes exert antioxidant/antiatherogenic effect. Additionally, our results provide strong evidence of the resin's antiatherogenic effect; therefore it is credited with beneficial health aspects.

Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways.

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.

The role of vitamin D receptor gene polymorphisms in the bone mineral density of Greek postmenopausal women with low calcium intake.

The aim of this study was to investigate the effect of common vitamin D receptor (VDR) gene polymorphisms on the bone mineral density (BMD) of Greek postmenopausal women. Healthy postmenopausal women (n=578) were recruited for the study. The BMD of the lumbar spine and hip was measured using dual-energy X-ray absorptiometry with the Lunar DPX-MD device. Assessment of dietary calcium intake was performed with multiple 24-h recalls. Genotyping was performed for the BsmI, TaqI and Cdx-2 polymorphisms of the VDR gene. The selected polymorphisms were not associated with BMD, osteoporosis or osteoporotic fractures. Stratification by calcium intake revealed that in the low calcium intake group (<680 mg/day), all polymorphisms were associated with the BMD of the lumbar spine (P<.05). After adjustment for potential covariates, BsmI and TaqI polymorphisms were associated with the presence of osteoporosis (P<.05), while the presence of the minor A allele of Cdx-2 polymorphism was associated with a lower spine BMD (P=.025). In the higher calcium intake group (>680 mg/day), no significant differences were observed within the genotypes for all polymorphisms. The VDR gene is shown to affect BMD in women with low calcium intake, while its effect is masked in women with higher calcium intake. This result underlines the significance of adequate calcium intake in postmenopausal women, given that it exerts a positive effect on BMD even in the presence of negative genetic predisposition.

Does a short breastfeeding period protect from FTO-induced adiposity in children?

CONTEXT: A number of studies have reported replicable associations between common genetic loci and obesity indices. One of these loci is the fat mass and obesity associated locus (FTO). We aimed to assess whether breastfeeding mediated the known association between FTO and indices of body fatness. METHODS: This study includes three independent pediatric cohorts, two of Greek origin (the Gene-Diet Attica Investigation: GENDAI, n=1 138 and the "Growth, Exercise and Nutrition Epidemiological Study In preschoolers": the GENESIS study, n=2 374) and one British (the Avon Longitudinal Study of Parents and Children:ALSPAC, n=4 325). Among other information, breastfeeding history was recorded. A DNA sample was ascertained by either blood or saliva. Genotyping for FTO variants was performed in GENDAI and ALSPAC for the rs9939609, while in GENESIS, for the rs17817449 variant. RESULTS: In all cohorts, multivariate analysis showed that the association between FTO:rs9939609 and measures of obesity was consistent across newly presented cohorts (GENDAI: Body mass index [BMI], ß=0.43, p=0.009; Waist Circumference, ß=1.067, p=0.019; triceps skinfold, ß=0.972, p=0.003; subscapular skinfold, ß=0.593, p=0.023; GENESIS: Waist Circumference, ß=0.473, p=0.008 and subscapular skinfold, ß=0.227, p=0.014). Inclusion of one month of breastfeeding as an interaction term effectively removed these associations with indices of obesity (BMI, Waist-Hip-Ratio and subscapular skinfold). No evidence of such interaction was observed for the independent cohort of British children. CONCLUSIONS: Our findings indicate that in two moderately sized Greek samples, breastfeeding may exert a modifying effect on the relationship between variants at the FTO locus and indices of adiposity. These findings were not replicated in a larger British collection.

Low-density lipoprotein receptor-related protein 5 polymorphisms are associated with bone mineral density in Greek postmenopausal women: an interaction with calcium intake.

The low-density lipoprotein receptor-related protein 5 (LRP5) has been shown to play a significant role in bone biology. This study aimed to assess the association of four common polymorphisms of the LRP5 gene with bone mineral density (BMD) and possible genexcalcium intake interactions in Greek postmenopausal women. For this observational cross-sectional association study, healthy postmenopausal women (N=578) were recruited (between December 2006 and January 2008) and genotyped for four polymorphisms (rs1784235, rs491347, rs4988321, and rs4988330) in the LRP5 gene. Measurements of BMD were performed and detailed medical, dietary, and anthropometric data were recorded. Student t tests and multiple linear regression models were applied after controlling for potential covariates (ie, age, weight, height, and calcium intake). None of the polymorphisms was associated with the presence of osteoporosis, fractures, and hip BMD. All polymorphisms were associated with unadjusted spine BMD, with the exception of rs4988330. Only rs4988321 was associated with adjusted spine BMD, where the presence of the A allele was associated with significantly lower spine BMD compared with the GG genotype (P=0.002). An interaction of the rs4988321 polymorphism with calcium intake (P=0.016) was found. The carriers of the A allele demonstrated significantly lower spine BMD compared to GG homozygotes (P=0.001) only in the lowest calcium intake group (<680 mg/day), whereas in the highest calcium intake group no differences were found in BMD between genotypes. These findings demonstrate that both rs4988321 polymorphism and its interaction with calcium intake are associated with BMD, whereas higher calcium intake was shown to decrease the negative effect of this polymorphism on BMD.

Apolipoprotein polymorphisms and familial hypercholesterolemia.

The majority of apolipoproteins known to play a major role in lipid metabolism were identified over 20 years ago, and nine of them (APOA1, -A2, -A4, -B48, -B100, -C1, -C2, -C3 and -E) have long been known to be most relevant to the regulation of lipoproteins. Polymorphisms of genes encoding apolipoproteins influence plasma levels of high-density lipoproteins (HDL), very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL) chylomicrons or triglycerides. Familial hypercholesterolemia (FH), an autosomal dominant disorder, is caused by mutations mainly located in the low-density lipoprotein receptor (LDLR) gene, or more rarely within the apolipoprotein B-100 gene or the gene encoding a secreted proteinase PSCK9. FH is characterized by elevated concentrations of LDL, deposition of LDL-derived cholesterol in tendons, skin xanthomas, and premature coronary artery disease. The frequency of heterozygotes is approximately one in 500 persons, placing FH among the most common inborn errors of metabolism. The risk of cardiovascular disease in these patients is influenced not only by the type of the mutations they carry, but also by the haplotype of lipid modifier genes, as is the case of apolipoproteins. In this review, we present current information that demonstrates the impact of apolipoprotein polymorphisms on the FH phenotype.

Natural antioxidant compounds in risk factors for CVD.

The benefits of drug treating hypertension, hyperglycemia and hyperlipidemias in terms of reduction of CVD morbidity and mortality are well established. However, there is epidemiological evidence that consumption of certain foods results to a reduction in myocardial infarction markers. Given in many reviews is the impact of dietary antioxidants pertained to LDL oxidation and to vascular endothelial dysfunction. The potential of a diet rich in these compounds on the management of hypertension, hyperglycemia and hyperlipidemias is hereby criticized. Although their clinical use not always translates into clinical benefit, data are motivating. In the future, these agents may be very important complementary treatment options for subjects with high risk for CVD.

Genes, diet and type 2 diabetes mellitus: a review.

Diabetes mellitus is widely recognized as one of the leading causes of death and disability. While insulin insensitivity is an early phenomenon partly related to obesity, pancreatic beta-cell function declines gradually over time even before the onset of clinical hyperglycemia. Several mechanisms have been proposed to be responsible for insulin resistance, including increased non-esterified fatty acids, inflammatory cytokines, adipokines, and mitochondrial dysfunction, as well as glucotoxicity, lipotoxicity, and amyloid formation for beta-cell dysfunction. Moreover, the disease has a strong genetic component, although only a handful of genes have been identified so far. Diabetic management includes diet, exercise and combinations of antihyperglycemic drug treatment with lipid-lowering, antihypertensive, and antiplatelet therapy. Since many persons with type 2 diabetes are insulin resistant and overweight, nutrition therapy often begins with lifestyle strategies to reduce energy intake and increase energy expenditure through physical activity. These strategies should be implemented as soon as diabetes or impaired glucose homoeostasis (pre-diabetes) is diagnosed.

Polymorphisms associated with apolipoprotein B levels in Greek patients with familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is a genetic disorder characterized by high low-density lipoprotein-cholesterol (LDL-C) concentrations, which frequently gives rise to premature coronary artery disease. The clinical expression of FH is highly variable, even in patients carrying the same LDL receptor (LDLR) gene mutation. This variability may be due to environmental and other genetic factors. METHODS: We investigated paraoxonase 2 (PON 2) Ser311Cys, lipoprotein lipase (LPL) Asn291Ser, plasminogen activator inhibitor-1 (PAI-1) T11053G, beta-fibrinogen (FGB) -455 G>A and nitric oxide synthase gene (NOS) -922 A>G polymorphisms in 84 patients with FH. The effect of polymorphisms as independent factors of high lipid values was evaluated. RESULTS: The PON 2 Cys311 allele was correlated with high total cholesterol and LDL-C and apolipoprotein B levels, while LPL Asn291, PAI-1 T11053, FGB -455 G and NOS -922 A alleles were correlated with high apolipoprotein B levels. CONCLUSIONS: These results suggest that apolipoprotein B levels in FH heterozygotes may be affected by several different genetic variants.

Natriuretic peptide Val7Met substitution and risk of coronary artery disease in Greek patients with familial hypercholesterolemia.

Atrial natriuretic peptide (ANP or NPPA) is the precursor protein of the form of amyloidosis called isolated atrial amyloid (IAA), which is related to the increased incidence of cardiac pathological conditions with age. Familial hypercholesterolemia (FH) patients are characterized by high concentrations of low-density lipoprotein cholesterol (LDL-C), which frequently gives rise to premature coronary artery disease (CAD). However, not all FH patients have the same clinical phenotype. The aim of the present study was to assess the relationship between ANP polymorphisms and apolipoprotein (Apo) A1 levels and CAD risk in FH patients. Transition T2238C, which leads to ANP with two additional arginines, and G664A (Val7Met) were investigated with lipid values and clinical phenotype in 83 FH patients. ApoA1 and HDL cholesterol levels were lower in GA patients compared to GG homozygotes for the G664A polymorphism. No association was found between the G664A polymorphism and CAD in our population. Moreover, ApoA1 and high-density lipoprotein cholesterol (HDL-C) levels did not differ among the different genotypes of the T2238C polymorphism, even after adjusting for age and sex. The 664A allele of the ANP polymorphism is associated with lower levels of ApoA1 and HDL-C in FH patients, but not with CAD risk. Concerning the T2238C polymorphism, no effect was found on lipid parameters or CAD incidence.