Socioeconomic position and education in patients with coeliac disease

Background and aimSocioeconomic position and education are strongly associated with several chronic diseases, but their relation to coeliac disease is unclear. We examined educational level and socioeconomic position in patients with coeliac disease.MethodsWe identified 29,096 patients with coeliac disease through biopsy reports (defined as Marsh 3: villous atrophy) from all Swedish pathology departments (n = 28). Age- and sex-matched controls were randomly sampled from the Swedish Total Population Register (n = 145,090). Data on level of education and socioeconomic position were obtained from the Swedish Education Register and the Occupational Register. We calculated odds ratios for the risk of having coeliac disease based on socioeconomic position according to the European Socioeconomic Classification (9 levels) and education.ResultsCompared to individuals with high socioeconomic position (level 1 of 9) coeliac disease was less common in the lowest socioeconomic stratum (routine occupations = level 9 of 9: adjusted odds ratio = 0.89; 95% confidence interval = 0.84–0.94) but not less common in individuals with moderately low socioeconomic position: (level 7/9: adjusted odds ratio = 0.96; 95% confidence interval = 0.91–1.02; and level 8/9: adjusted odds ratio = 0.99; 95% confidence interval = 0.93–1.05). Coeliac disease was not associated with educational level.ConclusionsIn conclusion, diagnosed coeliac disease was slightly less common in individuals with low socioeconomic position but not associated with educational level. Coeliac disease may be unrecognised in individuals of low socioeconomic position.     

Prevalence and risk factors for diabetic microvascular complications in newly diagnosed type II diabetes mellitus. Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetic Study (SN-DREAMS, report 27)

PurposeThe aims of this study were to report the prevalence of various microvascular complications and to identify the various clinical and biochemical characteristics related to these complications in subjects with newly diagnosed type II diabetes.MethodsOf the 5999 subjects enumerated, 1414 subjects with diabetes (both known and newly diagnosed) were analyzed for the study. Among the diabetic subjects, 248 (17.5%) were newly diagnosed with diabetes and the remaining had history of diabetes. All subjects underwent a detailed standard evaluation to detect diabetic retinopathy (fundus photography), neuropathy (vibration pressure threshold), and nephropathy (microalbuminuria).ResultsThe prevalence of any form of microvascular complication was 30.2% (95% confidence interval [CI] = 24.5–35.9). The prevalence of diabetic retinopathy was 4.8%, and that of diabetic nephropathy and neuropathy was 10.5%. The risk factors for developing any form of microvascular complication were increasing age (odds ratio [OR] = 1.07, 95% CI = 1.04–1.11, P < .0001), increasing systolic blood pressure (OR = 1.03, 95% CI = 1.01–1.06, P = .001), and increasing hemoglobin (OR = 1.39, 95% CI = 1.09–1.79, P = .011). The risk factors for diabetic retinopathy and diabetic nephropathy were increasing systolic blood pressure (OR = 1.06 [P = .001] for retinopathy and OR = 1.04 [P = .012] for nephropathy) and increasing hemoglobin (OR = 2.20 [P = .007] for retinopathy and OR = 1.57 [P = .023] for nephropathy). The risk factor for diabetic neuropathy was increasing age (OR = 1.12, P < .0001).ConclusionsNearly one third of the newly diagnosed type II diabetes subjects had some form of microvascular complication; nephropathy, and neuropathy being commoner than retinopathy.     

Serum uric acid concentration is associated with worsening in severity of diabetic retinopathy among type 2 diabetic patients in Taiwan—A 3-year prospective study

AimsTo explore the role of serum uric acid (SUA) concentration in diabetic retinopathy (DR) for patients with type 2 diabetes mellitus (T2DM).MethodsA 3-year prospective study in 749 patients with T2DM and without proliferative diabetic retinopathy (PDR) was conducted at a medical center. Baseline SUA concentration and parameters of glycemic control, blood pressure, kidney disease, and lipid profiles were analyzed to determine their contribution to DR.ResultsFundus examination showed that 184 patients (24.6%) had non-proliferative retinopathy and 565 (75.4%) without DR at baseline. After 3 years, increase in the severity of DR was recognized in 103 patients (13.8%), including 81 patients with newly developed DR. Patients with increase in severity of DR positively associated with duration of DM (11.9 vs. 9.4 years, p = 0.001), HbA1c (7.6 vs. 7.2%, p = 0.001), albuminuria (45.5 vs. 31.0%, p = 0.006), and SUA (6.47 vs. 5.87 mg/dl, p < 0.001) than did those without change in DR stage. Cox regression showed that patients with SUA in the 3rd (5.9–6.9 mg/dl) and 4th (≥7.0 mg/dl) quartiles had hazard ratios for DR worsening of 2.57 and 3.66 (95% C.I. 1.30–5.08 and 1.92–7.00) when compared with patients with SUA in the 1st quartile (<4.9 mg/dl).ConclusionsSUA concentration is associated with the increase in severity of DR over a 3-year period in patients with T2DM. Further study is required to define the exact role of SUA in DR.     

A study of the 3-year incidence of diabetic retinopathy in a French diabetic population seen at Lariboisière Hospital, Paris

AimThis study evaluated the incidence of diabetic retinopathy (DR) over a 3-year period in a French population that was followed by OPHDIAT^®, and assessed the clinical and biological risk factors associated with incident retinopathy.MethodsThe studied patients were screened for DR during hospitalization for their annual diabetes check-up in the endocrinology department by two examinations three years apart. DR screening used the OPHDIAT^® telemedical network, and the examination included clinical and biological data.ResultsA total of 254 patients were studied. At the 3-year follow-up, the incidence was 14.0%, (CI: 9.5–18.4%). Longer duration of diabetes and the presence of micro- or macroalbuminuria were significantly associated with incident retinopathy (P < 0.05). Other potential risk factors were not statistically significantly related to DR progression, and only treatment with insulin showed a trend towards significance (P < 0.20).ConclusionThis study provides the first French data on the incidence of DR, which was estimated after a 3-year follow-up at 14.0%. Longer duration of time from the onset of diabetes and higher baseline albuminuria were the only statistically significant risk factors found for the incidence of DR after our 3-year study. Nevertheless, microalbuminuria should be more widely used in ophthalmological practice in the assessment of DR, as is already the case for both blood pressure and HbA_1c.     

The -250G/A polymorphism in the hepatic lipase gene promoter influences the postprandial lipemic response in healthy men

Background and aimThe −250G/A promoter polymorphism of the hepatic lipase gene has been associated with changes in the activity of the enzyme. We investigated whether this polymorphism modifies the postprandial response of triacylglycerol-rich lipoproteins (TRL) in young normolipemic males.Methods and resultsFifty-one healthy apolipoprotein (apo) E3/E3 male volunteers (30 G/G and 21 carriers of the A allele) underwent a vitamin A fat-loading test and blood samples were drawn every hour until the 6th, and every 2 h and 30 min until the 11th. Total plasma cholesterol and triacylglycerols (TG), as well as cholesterol, TG and retinyl palmitate (RP) in TRL, isolated by ultracentrifugation, were determined.Carriers of the A allele showed a higher response (P = 0.008), a higher area under the curve (AUC; P = 0.022) and a lower RP peak time (P = 0.029) in small TRL during the postprandial response, as well as a lower peak time in total plasma TG levels (P = 0.034) and large TRL-TG (P = 0.033) than subjects who were homozygous for the G allele.ConclusionOur data indicate that the presence of the A allele in the −250G/A promoter polymorphism of the hepatic lipase gene is associated with a higher postprandial lipemic response.     

A study in three European IBD cohorts confirms that the ATG16L1 c.898A > G (p.Thr300Ala) variant is a susceptibility factor for Crohn’s disease

Background and aimsA recent study reported that a nonsynonymous SNP rs2241880 (c.898A > G, p.Thr300Ala) within ATG16L1 confers susceptibility to Crohn's disease (CD). We analyzed ATG16L1 c.898A > G in three independent European inflammatory bowel disease (IBD) cohorts from Germany, Hungary and the Netherlands.MethodsIn total, we included 910 European IBD patients and compared the ATG16L1 c.898A > G genotype frequency with 707 ethnically matched healthy controls. We included patients from 3 populations originating from Germany (CD n = 310; ulcerative colitis [UC] n = 179), Hungary (CD n = 147; UC n = 117), and the Netherlands (CD n = 157). Subtyping analysis was performed in respect to CARD15 alterations and clinical characteristics.ResultsWe found a highly significant association of c.898A > G to CD. The association was significant (p = 0.0005) for the total CD cohort but also for the individual populations from Germany (p = 0.02) and Netherlands (p = 0.02) whereas in the Hungarian CD patients a clear trend was observed (p = 0.19; OR 1.227, 95% CI 0.910; 1.654). No association was found between c.898A > G and UC. No statistical interactions were observed between ATG16L1 c.898A > G and CARD15 variants. Furthermore no association to a CD subphenotype was detected.ConclusionsWe confirm that ATG16L1 variant c898A > G confers a risk variant for CD but is not associated with a distinct CD phenotype.     

The epistasis between vascular homeostasis genes is apparent in essential hypertension

ObjectiveThe epistasis influence of vascular homeostasis genes is vital to multigenetic diseases. This study was designed to perceive the possible role of epistasis in the etiology of essential hypertension.MethodsWe investigated seven polymorphisms of ACE, CYP11B2 and NOS3 epistatically, and SBP, DBP, MAP, ACE activity, plasma aldosterone concentration (PAC) and NOx level in 860 age- and ethnicity-matched unrelated north-Indian subjects.ResultsThe hypertension risk in individuals with interacted-genotypes (IwIw + IwIc) + (4aa), (IcIc) + (4bb + 4ba) and IcIc + 4aa of the CYP11B2 and NOS3 was significantly higher with odds ratio 5.5 (95% CI = 2.9–10.6, P < 0.0001), 2.4 (95% CI = 1.4–4.1, P < 0.0008) and 7.5 (95% CI = 1.6–34.8, P = 0.010), respectively. The odds ratio for hypertension with interacted-haplotypes (?344T/Ic) + (?922A/?786T/4a/894G) and (?344T/Ic) + (?922G/?786C/4a/894G) of CYP11B2 and NOS3 was 5.3 (95% CI = 2.0–14.2, P = 0.005) and 3.9 (95% CI = 1.4–10.4, P = 0.04), respectively; whereas for the protective interacted-haplotypes (?344T/Iw) + (?922A/?786T/4b/894G), the odds ratio was 0.7 (95% CI = 0.5–0.9, P = 0.03). While the interacted-genotypes, IcIc + 4aa correlated with higher SBP and MAP (P = 0.006; P = 0.04), the interacted-haplotypes, (?344T/Ic) + (?922A/?786T/4a/894G) and (?344T/Ic) + (?922G/?786C/4a/894G) correlated with higher MAP and lower NOx level (P = 0.02 and P = 0.03, respectively), and the protective interacted-haplotypes (?344T/Iw) + (?922A/?786T/4b/894G) correlated with lower PAC and MAP (P = 0.024 and P = 0.018, respectively).ConclusionsThe epistasis between CYP11B2 and NOS3 and its correlation with varied clinical and biochemical parameters signify its possible contribution in the complex etiology of hypertension.     

The relationships between type 2 diabetic retinopathy and VEGF-634G/C and VEGF-460C/T polymorphisms in Han Chinese subjects

ObjectiveTo investigate how VEGF-634G/C and VEGF-460C/T SNPs are related to diabetic retinopathy (DR) in Han Chinese subjects from the Shijiazhuang region of China.MethodsTotally 376 DM cases were divided into non-proliferative diabetic retinopathy (NPDR) group (n = 124), proliferative diabetic retinopathy (PDR) group (n = 108), and diabetes without retinopathy (DWR) group (n = 144). PCR/LDRwas utilised to detect and assess the genotypes and allele distribution frequencies at the VEGF-634G/C and VEGF-460C/T loci in each group.ResultsThe differences between NPDR, PDR and DWR groups were not significant in genotypes and allele distribution frequencies at VEGF-634G/C locus (P > 0.05). But there were significant differences between NPDR and DWR groups in genotypes (P = 0.013) and allele distribution frequencies (P = 0.002) at VEGF-460C/T locus, at which CT + CC genotypes were associated with a reduced risk of developing NPDR. There were no significant differences in genotypes (P = 0.759) or allele distribution frequencies (P = 0.433) at VEGF-460C/T locus between PDR and DWR groups.ConclusionsAmong Chinese Han individuals with type-2 DM, polymorphism − 634G/C of the VEGF gene was not correlated with NPDR or PDR; however, polymorphism-460C/T of the VEGF gene was correlated with NPDR, and C allele was associated with lower NPDR risk than T allele.     

Adiponectin G276T gene polymorphism is associated with cardiovascular disease in Japanese patients with type 2 diabetes

ObjectiveAdiponectin has anti-atherogenic properties and reduced serum adiponectin levels are associated with cardiovascular disease (CVD). In this study, we examined the relationship between CVD and adiponectin (ADIPOQ) gene G276T polymorphism that is associated with serum adiponectin level in a large cohort of type 2 diabetic patients.Research design and methodsWe enrolled 2637 Japanese type 2 diabetic subjects (males, 61.1%; age, 54.9 ± 7.9 years old), determined their genotypes regarding ADIPOQ G276T polymorphisms, and evaluated the association between this polymorphism and the prevalence of CVD (myocardial infarction and/or cerebral infarction).ResultsThe prevalence of CVD tended to be higher as the number of G alleles increased [GG (9.5%), GT (6.8%), TT (5.6%), p value for trend = 0.0059] and was significantly higher in the subjects with GG genotype compared to those with GT or TT genotype (9.5% vs. 6.6%, p = 0.0060). Multiple logistic regression analyses revealed that the number of G alleles (Odds ratio (OR) = 1.49 with 95%CI 1.09–2.05, p = 0.0125) and GG genotype (OR = 1.66 with 95%CI 1.13–2.43, p = 0.0098) were significantly associated with CVD even after adjustment for conventional risk factors. Interestingly, the presence of obesity further and significantly increased the risk of CVD in the subjects with GG genotype (OR = 1.67 with 95%CI 1.14–2.44, p = 0.0090) but not in the subjects with TT or GT genotype (OR = 1.17 with 95%CI 0.73–1.89, NS).ConclusionsIt is likely that the G allele of the ADIPOQ G276T polymorphism is a susceptibility allele for CVD in Japanese type 2 diabetic patients, especially when they accompany obesity.     

C-reactive protein is directly related to plasminogen activator inhibitor type 1 (PAI-1) levels in diabetic subjects with the 4G allele at position -675 of the PAI-1 gene

Background and aimsC-reactive protein (CRP) has been identified as a possible factor able to promote atherosclerosis. “In vitro” studies have demonstrated that CRP induces plasminogen activator inhibitor type 1 (PAI-1) expression, suggesting a hypofibrinolytic role for CRP. As CRP and PAI-1 levels increase in type 2 diabetic subjects, we decided to study the relationship between CRP and PAI-1, and the role of the 4G/5G polymorphism of the PAI-1 gene on this relationship in a diabetic population without complications.Methods and resultsTwo hundred and ninety-five type 2 diabetic patients (age 60.9 ± 10.5 years) and 290 healthy controls (age 59.2 ± 11.5 years) were enrolled. A significant correlation between PAI-1 and CRP in diabetic subjects was found (r = 0.45, p < 0.001), whereas no relationship was evident in the control subjects between these inflammatory markers. Multiple regression analysis highlighted that CRP is the only one significant variable of PAI-1 antigen in diabetic subjects (partial r = 0.31, p < 0.01). Stratifying by genotype, a positive correlation between PAI-1 and CRP in 4G/4G (partial r = 0.64 p < 0.001) and 4G/5G (partial r = 0.47, p < 0.001) subjects was found, whereas no correlation in 5G/5G was present. Multiple regression analysis confirmed the presence of this correlation in 4G/4G (partial r = 0.45, p < 0.001) and in 4G/5G (partial r = 0.34, p = 0.007) diabetic patients.ConclusionsThese findings demonstrate that CRP plays an important role in the complex mechanism regulating PAI-1 antigen in 4G diabetic carriers.     

Serum fibroblast growth factor 21 concentrations in type 2 diabetic retinopathy patients

Aims/purposeFibroblast growth factor 21 (FGF21) is a major metabolic regulator in the body that has been shown to be elevated in a number of metabolic disturbances including type 2 diabetes mellitus (T2DM) and the metabolic syndrome. However, little is known regarding the circulating levels of FGF21 in type 2 diabetic retinopathy (T2DR) and its association with the severity of the condition.MethodsIn a cross-sectional setting, 142 individuals, consisting of (1) T2DM patients without T2DR, (2) T2DM patients with T2DR, and (3) healthy control subjects were recruited for this study. Various clinical and biochemical parameters were assessed and entered for analysis.ResultsSerum FGF21 levels were significantly elevated in T2DM subjects without retinopathy (103.50 [75.75] pg/mL) compared with healthy controls (99.00 [126.75] pg/mL). Circulating FGF21 levels were comparable across different stages of T2DR (233.00 [109.00] for nonproliferative type 2 diabetic retinopathy [NPT2DR] vs. 215.00 [122.00] for proliferative type 2 diabetic retinopathy [PT2DR] groups, P = 361). FGF21, triglycerides, and duration of diabetes mellitus were significantly associated with T2DM in baseline models. However, after adjustment for potential confounders, in the final multivariate model, FGF21 emerged as the only significant factor associated with T2DM (OR = 13.772, 95% CI = 3.062–61.948, P = 001).ConclusionsSerum FGF21 concentrations are markedly elevated in patients with T2RN. The association between FGF21 and T2DR appears to be independent of the effects of potential confounding variables. These findings may suggest FGF21 as a novel surrogate diagnostic biomarker in initial stages of T2DR (particularly with FGF21 values above 135.5 pg/mL).     

Does bariatric surgery adversely impact on diabetic retinopathy in persons with morbid obesity and type 2 diabetes? A pilot study

AimsTo assess the incidence and progression of diabetic retinopathy (DR) 12 months post bariatric surgery in persons with morbid obesity and type 2 diabetes.MethodsA retrospective pilot analysis of electronic hospital records between 1998 and 2012.Results40 of 148 subjects had pre- and post-surgery DR screening. Of those without DR pre-surgery 1.5% (n = 26) progressed to minimum background DR (BDR) post surgery. Those with minimum BDR (n = 9) pre-surgery revealed no progression, with 55.6% (n = 5) showing evidence of regression. One person with moderately severe BDR and two with pre-proliferative DR (PPDR) prior to surgery experienced progression. Two persons with PPDR prior to surgery remained under the hospital eye services and were therefore not eligible to be re-assessed by the screening service.ConclusionsThere was a low incidence of new DR and progression of DR in those either without evidence of retinopathy or with minimal BDR prior to surgery with some subjects showing evidence of regression. There was however a risk of progression of DR in those with moderate BDR or worse, and should therefore be monitored closely post-surgery.     

Relation between plasma homocysteine, gene polymorphisms of homocysteine metabolism-related enzymes, and angiographically proven coronary artery disease

BackgroundHyperhomocyteinemia (HHcy) is a risk factor for coronary artery disease (CAD), and methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) polymorphisms may contribute to plasma total homocysteine (tHcy) variation. We investigated the association of polymorphisms 1298A→C in the MTHFR gene, 2756A→G in the MTR gene, and 66A→G in the MTRR gene with tHcy levels and with CAD in patients undergoing coronary angiography.MethodsCAD patients (n = 151) and control subjects (n = 79) were compared regarding the prevalence of the polymorphisms, risk factors, and biochemical parameters.ResultsThe mean tHcy concentration was significantly higher in CAD patients than in control subjects (P < 0.001). HHcy (tHcy ≥ 15 μmol/l) conferred an OR of CAD of 4.1 (95% CI 2.2–7.5, P < 0.001). In both cases and controls, smokers had a higher tHcy level than non-smokers and demonstrated a markedly increased risk for CAD (OR = 2.5, 95% CI 1.7–3.3, P < 0.001). The allele frequencies of the MTHFR 1298A→C, MTR 2756A→G, and MTRR 66A→G mutations were 36.7%, 15.7%, and 36.6%, respectively. The 1298C allele frequency was significantly higher in the CAD group than in controls (P < 0.05) and showed a significant association with CAD in heterozygote carriers. There was no statistically significant difference between cases and controls in the frequencies of the A2756G alleles/genotypes in the MTR gene and of the A66G alleles/genotypes in the MTRR gene. The contributions to tHcy levels of the three common mutations were statistically significant. The heterozygosity of the MTHFR 1298AC genotype, MTR 2756G allele, and MTRR 66G allele yielded an OR of 3.4, 2.0, and 2.1, respectively, for having HHcy.ConclusionWe suggest that HHcy confers a risk for CAD, and smokers with tHcy are at a greatly increased risk. Our finding supports an important role of the MTHFR gene in CAD and provides evidence of polygenic regulation of tHcy.     

Sensitivity of A1C to diagnose diabetes is decreased in high-risk older Southeast Asians

ObjectiveTo determine the effect of ageing on the performance of glycosylated haemoglobin A1C (A1C) for the diagnosis of diabetes mellitus (DM) in Southeast Asians.MethodsA1C was measured in 511 subjects (mean age of 52.4 years; range 14–93) undergoing the 75-g oral glucose tolerance test (OGTT). Using receiver operating curve (ROC) analysis, the performance of A1C for the diagnosis of diabetes (using different standard criteria) was compared between 4 groups: < 45 (n = 156), 45–54 (n = 132), 55–64 (n = 122), ≥ 65 years (n = 101).ResultsSubjects aged ≥ 65 years had the highest false-negative rates with fasting plasma glucose (60.8%) and A1C (35.1%), the smallest area under ROC curve (0.723, 95% CI 0.627–0.820), the lowest sensitivity (58.7%, 95% CI 50.4–65.7) and specificity (71.1%, 95% CI 57.3–82.6) of A1C 6.5%, compared to the younger age groups.ConclusionOGTT is preferable for diagnosis of DM in older Southeast Asian adults.     

Late afternoon blood pressure increase is associated with diabetic retinopathy in normotensive type 2 diabetes mellitus patients

AimsTo identify if the variability of blood pressure (BP) is associated with diabetic retinopathy (DR) in normotensive type 2 DM patients.MethodsSixty-five normotensive type 2 DM patients that had 24-h ambulatory BP monitoring (ABPM) were grouped according any degree of DR.ResultsFourteen (21%) patients had DR. Office BP and 24-h BP parameters did not differ between groups. At late afternoon period, patients with DR had higher increment in both systolic (11.3 ± 12.7 mmHg vs. 1.0 ± 11.4 mmHg, P = 0.006) and diastolic (6.7 ± 8.6 mmHg vs. ?0.73 ± 10.0 mmHg, P = 0.017) BP levels than those without. Multivariate logistic analyses were performed with DR as a dependent variable. Each 1 mmHg increment in systolic BP at the late afternoon period was associated with a 10.2% increase in DR prevalence [OR 1.102 (CI 95% 1.011–1.202, P = 0.027)], after adjustments for A1C test, DM duration, age, albuminuria and current smoking.ConclusionsIn conclusion, in normotensive type 2 DM patients, BP increase at late afternoon is associated to DR independently from confounder factors or other ABPM parameters.     

ADAM17_i33708A > G polymorphism interacts with dietary n-6 polyunsaturated fatty acids to modulate obesity risk in the Genetics of Lipid Lowering Drugs and Diet Network study

Background and aimsThe disintegrin and metalloproteinase ADAM17, also known as tumor necrosis factor alpha converting enzyme, is expressed in adipocytes. Importantly, elevated levels of ADAM17 expression have been linked to obesity and insulin resistance. Therefore, the aim of this study was to evaluate the association of six ADAM17 single nucleotide polymorphisms (SNPs) (m1254A > G, i14121C > A, i33708A > G, i48827A > C, i53440C > T, and i62781 G > T) with insulin-resistance phenotypes and obesity risk, and their potential interactions with dietary polyunsaturated fatty acids (PUFA).Methods and resultsADAM17 SNPs were genotyped in 936 subjects (448 men/488 women) who participated in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. Anthropometrical and biochemical measurements were determined by standard procedures. PUFA intake was estimated using a validated questionnaire. G allele carriers at the ADAM17_m1254A > G polymorphism exhibited significantly higher risk of obesity (P = 0.003), were shorter (P = 0.017), had higher insulin (P = 0.016), and lower HDL-C concentrations (P = 0.027) than AA subjects. For the ADAM17_i33708A > G SNP, homozygotes for the A allele displayed higher risk of obesity (P = 0.001), were heavier (P = 0.011), had higher BMI (P = 0.005), and higher waist measurements (P = 0.023) than GG subjects. A significant gene-diet interaction was found (P = 0.030), in which the deleterious association of the i33708A allele with obesity was observed in subjects with low intakes from (n-6) PUFA (P < 0.001), whereas no differences in obesity risk were seen among subjects with high (n-6) PUFA intake (P > 0.5)ConclusionThese findings support that ADAM17 (m1254A > G and i33708A > G) SNPs may contribute to obesity risk. For the ADAM17_i33708A > G SNP, this risk may be further modulated by (n-6) PUFA intake.     

Evaluation of subclinical atherosclerosis by computed tomography coronary angiography and its association with risk factors in familial hypercholesterolemia

ObjectiveTo investigate the association of four common single nucleotide polymorphisms (SNPs) at ABCG5 (i7892A>G, i18429C>T, Gln604GluC>G, i11836G>A) and five at ABCG8 (5U145T>G, Tyr54CysA>G, Asp19HisG>C, i14222T>C, and Thr400LysG>T) with plasma lipids concentrations and to explore the interaction between those SNPs and smoking in patients with FH.Methods and ResultsABCG5/G8 SNPs were genotyped in 500 subjects with genetic diagnosis of FH. Carriers of the minor A allele at the ABCG5_i11836G>A SNP displayed significantly higher HDL-C concentrations (P = 0.023) than G/G subjects. In addition, carriers of the minor G allele at the ABCG5_Gln604GluC>G SNP had significantly lower VLDL-C (P = 0.011) and lower TG (P = 0.017) concentrations than homozygous C/C. Interestingly, a significant gene-smoking interaction was found, in which carriers of the minor alleles at ABCG5 (i7892A>G, i18429C>T, i11836G>A) SNPs displayed significantly lower HDL-C, higher TC and higher TG respectively, only in smokers. On the other hand, nonsmokers carriers of the minor alleles at ABCG5 (i18429C>T and Gln604GluC>G) SNPs had significantly lower TG concentrations (P = 0.012 and P = 0.035) compared with homozygous for the major allele.ConclusionsOur data support the notion that ABCG5/G8 genetic variants modulate plasma lipids concentrations in patients with FH and confirm that this effect could be influenced by smoking. Therefore, these results suggest that gene-environmental interactions can affect the clinical phenotype of FH.     

Pulmonary arterial hypertension in congenital heart disease: an epidemiologic perspective from a Dutch registry

BackgroundPulmonary arterial hypertension (PAH) associated with congenital heart disease is usually the result of a large systemic-to-pulmonary shunt, and often leads to right ventricular failure and early death. The purpose of this study was to determine the prevalence of PAH among adult patients included in a national registry of congenital heart disease and to assess the relation between patient characteristics and PAH.MethodsPatients with PAH associated with a septal defect were identified from the registry. Gender, age, underlying diagnosis, previous closure, age at repair and NYHA classification were recorded. PAH was defined as a systolic pulmonary arterial pressure (sPAP) greater than 40 mm Hg, estimated by means of echocardiographical evaluation.ResultsThe prevalence of PAH among all 5970 registered adult patients with congenital heart disease was 4.2%. Of 1824 patients with a septal defect in the registry, 112 patients (6.1%) had PAH. Median age of these patients was 38 years (range 18–81 years) and 40% were male. Of these patients, 58% had the Eisenmenger syndrome. Among the patients with a previously closed septal defect, 30 had PAH (3%). Ventricular septal defect (VSD) was the most frequent underlying defect (42%) among patients with PAH and a septal defect. Female sex (Odds ratio = 1.5, p = 0.001) and sPAP (Odds ratio = 0.04, p < 0.001) were independently associated with a decreased functional class.ConclusionPAH is common in adult patients with congenital heart disease. In our registry the prevalence of PAH in septal defects is around 6%. More than half of these patients have the Eisenmenger syndrome, which accounts for 1% of the total population in the CONCOR registry. Whether the prevalence of PAH will decrease in the future as a result of early detection and intervention remains to be awaited.     

SREBP-2 and SCAP isoforms and risk of early onset myocardial infarction

BackgroundCholesterol metabolism is mediated, in part, by the sterol-regulatory element binding proteins (SREBPs) that are activated by a SREBP cleavage-activating protein (SCAP). We examined whether coding variations in the interacting domains of both genes, are related to early-onset MI risk in a population-based case-control study from western Washington State.MethodsCases were 257 women, aged 18–59 years, and 320 men, aged 18–49 years, with first acute non-fatal MI; controls were 353 women and 311 men, similar in age, identified from the community who had no history of clinical CHD or stroke. Genotyping of the SREBF-2 G1784C polymorphism (SREBP-2-595A/G isoforms), and the SCAP A2386G polymorphism (SCAP-796I/V isoforms), were performed.ResultsAfter adjustment for age and race, the SREBP-2-595A isoform was associated with increased MI risk among men (OR = 1.63, 95% CI = 1.26–2.12). In contrast, there was little evidence for an association among women in a multiplicative model. However, compared to SREBP-2-595G homozygotes, homozygote women for the SREBP-2-595A isoform were at nearly two-fold increased risk (OR = 1.95, 95% CI = 1.07–3.54). Overall, SCAP genotypes were neither associated with MI in men nor in women. However, in men, SCAP genotypes were found to modify the association between SREBF-2 and MI (p-value for interaction = 0.01).ConclusionThe SREBP-2-595A isoform was associated with an increased risk of early-onset MI in U.S. men. The SCAP polymorphism appeared to modify the associations of SREBF-2 genotype with MI risk among men. These novel findings require confirmation in other populations.     

Colorectal stenting as a bridge to surgery reduces morbidity and mortality in left-sided malignant obstruction: a predictive risk score-based comparative study

BackgroundThe Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity model, and its Portsmouth and colorectal modifications are used to predict postoperative mortality and morbidity after colorectal surgery.AimsTo compare stent placement as a bridge to surgery vs. emergency surgical resection in patients with acute left-sided colorectal cancer obstruction using P-POSSUM and CR-POSSUM.MethodsFrom January 2008 to December 2009, the physiological and operative scores, morbidity and mortality predicted by the P-POSSUM and CR-POSSUM scores were collected in all consecutive patients with LCCO who underwent surgical resection directly (Group A) or after stent placement (Group B).ResultsEighty-six patients were enrolled (Group A-41 and Group B-45). The observed 30-day mortality rate was 9.8% (4/41) in Group A and 2.4% (1/45) in Group B. The 30-day morbidity rate was 61% (25/41) in Group A and 29% (13/45) in Group B. The mean values of P-POSSUM morbidity (A = 70.5% vs. B = 34.3%; p = 0.001), P-POSSUM mortality (A = 13.6% vs. B = 2.4%; p = 0.001) and CR-POSSUM mortality (A = 15.1% vs. B = 4.9%; p = 0.001) were significantly lower in the Group B patients than in the Group A patients.ConclusionsBridge to surgery strategy reduces the surgical risks in LCCO, and P-POSSUM and CR-POSSUM scores represent a good tool for comparing the two strategies.