Association of apolipoprotein A5 gene variants with metabolic syndrome in Tunisian population

Aim of the studyAPOA5 has been linked to metabolic syndrome (MetS) or its traits in several populations. In North Africa, only the Moroccan population was investigated. Our aim is to assess the association between APOA5 gene polymorphisms with the susceptibility to MetS and its components in the Tunisian population.Materials and methodsA total of 594 participants from the Tunisian population were genotyped for two polymorphisms rs3135506 and rs651821 located in APOA5 gene using KASPar technology. Statistical analyses were performed using R software.ResultsThe SNP rs651821 increased the risk of MetS under the dominant model (OR = 1.91 [1.17–3.12], P = 0.008) whereas the variant rs3135506 was not associated with MetS. After stratification of the cohort following the sex, only the variant rs651821 showed a significant association with MetS among the women group. The influence of the geographic origin of the studied population on the genotype distribution of APOA5 variants showed that the variant rs651821 was significantly associated with MetS only for the Northern population. The association analyses of the variants rs651821 and rs3135506 with different quantitative traits of MetS showed a significant association only between the variant rs3135506 and triglycerides levels.ConclusionThis is the first study reporting the association of APOA5 gene variants with MetS in Tunisia. Our study emphasizes the role of APOA5 variants in the regulation of the triglycerides blood levels. Further studies are needed to confirm the clinical relevance of these associations and to better understand the physiopathology of the MetS.     

The effect of a novel intergenic polymorphism (rs11774572) on HDL-cholesterol concentrations depends on TaqIB polymorphism in the cholesterol ester transfer protein gene

Background and aimsSeveral genes have been shown to individually affect plasma lipoprotein metabolism in humans. Studies on gene–gene interactions could offer more insight into how genes affect lipid metabolism and may be useful in predicting lipid concentrations. We tested for gene–gene interactions between TaqIB SNP in the cholesterol ester transfer protein (CETP) and three novel single nucleotide polymorphisms (SNPs), namely rs11774572, rs7819412 and rs6995374 for their effect on metabolic syndrome (MetS) components and related traits.Methods and resultsThe aforementioned SNPs were genotyped in 1002 subjects who participated in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. Lipids were measured by standard procedures and lipoprotein subfractions, by proton nuclear magnetic resonance spectroscopy. Polymorphism rs11774572 was significantly associated with MetS (P = 0.020), mainly driven by the association of the C allele with lower HDL-C (P = 0.043) and higher triglycerides (P = 0.049) and insulin (P = 0.040) concentrations than TT subjects. A significant interaction between SNPs rs11774572 and CETP-TaqIB SNPs was found for HDL-C concentrations (P = 0.006) and for HDL (P = 0.008) and LDL particle sizes (P = 0.009), small LDL (P = 0.004), and VLDL concentrations (P = 0.021), in which TT homozygotes displayed higher HDL-C concentrations and for HDL and LDL particle sizes, and lower small LDL and VLDL concentrations than C carriers, if they were CETP B2 allele carriers (P values ranging from <0.001 to 0.001).ConclusionsThe rs11774572 polymorphism may play a role in the dyslipidemia that characterizes MetS. The interaction between rs11774572 and CETP-TaqIB SNPs on HDL-C concentrations provides some insights into the underlying mechanisms.     

Gene-nutrient interactions and gender may modulate the association between ApoA1 and ApoB gene polymorphisms and metabolic syndrome risk

ObjectiveDyslipidemia is a key feature of the metabolic syndrome (MetS), which is determined by both genetic and dietary factors.MethodsWe determined the relationships between ApoA1 and ApoB polymorphisms and MetS risk, and whether dietary fat modulates this in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n = 1754).ResultsApoB rs512535 and ApoA1 rs670 major G allele homozygotes had increased MetS risk (OR 1.65 [CI 1.24, 2.20], P = 0.0006; OR 1.42 [CI 1.08, 1.87], P = 0.013), which may be, partly, explained by their increased abdominal obesity and impaired insulin sensitivity (P < 0.05) but not dyslipidemia. Interestingly these associations derived primarily from the male GG homozygotes (ApoB rs512535 OR 1.92 [CI 1.31, 2.81], P = 0.0008; ApoA1 rs670 OR 1.50 [CI 1.05, 2.12], P = 0.024). MetS risk was exacerbated among the habitual high-fat consumers (>35% energy) (ApoB rs512535 OR 2.00 [CI 1.14, 3.51], P = 0.015; OR 1.58 [CI 1.11, 2.25], P = 0.012 for ApoA1 rs670). In addition a high monounsaturated fat (MUFA) intake (>14% energy) increased MetS risk (OR 1.89 [CI 1.08, 3.30], P = 0.026 and OR 1.57 [CI 1.10, 2.40], P = 0.014 for ApoB rs512535 and ApoA1 rs670, respectively). MetS risk was abolished among the habitual low-fat consumers (<35% energy). Saturated and polyunsaturated fat intake did not modulate MetS risk.ConclusionApoB rs512535 and ApoA1 rs670 may influence MetS risk. Apparent modulation of these associations by gender and dietary fat composition suggests novel gene-gender-diet interactions.     

T-cadherin gene variants are associated with type 2 diabetes and the Fatty Liver Index in the French population

AimAdiponectin is an adipocyte-secreted protein associated with insulin sensitivity. T-cadherin is a receptor for high and medium molecular weight adiponectin. In GWAS, T-cadherin gene (CDH13) polymorphisms are associated with circulating adiponectin levels. This study investigated the associations between genetic variants of CDH13 and type 2 diabetes (T2D), and its related parameters, in a Caucasian population.MethodsTwo polymorphisms of CDH13 (rs11646213 and rs3865188) were genotyped in two French cohorts, a general population from the D.E.S.I.R. study (n = 5212) and people with T2D in the DIABHYCAR study (n = 3123). Baseline adiponectin levels were measured in D.E.S.I.R. participants who were normoglycaemic at baseline, but hyperglycaemic after 3 years (n = 230), and in controls who remained normoglycaemic (n = 226) throughout.ResultsIn a cross-sectional analysis, CDH13 genotype distributions differed between those with and without T2D, with T2D odds ratios (OR) of 1.11 (95% CI: 1.04–1.18; P = 0.001) and 0.92 (95% CI: 0.87–0.98; P = 0.01) for rs11646213 and rs3865188, respectively. The rs11646213 variant, associated with a higher OR for T2D, was also associated with higher BMI (P = 0.03) and HbA_1c (P = 0.006), and lower plasma adiponectin levels (P = 0.03) in the D.E.S.I.R. participants. Conversely, the rs3865188 variant, associated with a lower OR for T2D, was also associated with lower BMI (P = 0.03), HbA_1c (P = 0.02) and Fatty Liver Index (FLI; P ≤ 0.01), and higher plasma adiponectin levels (P = 0.002). Associations with HbA_1c, FLI and adiponectin levels persisted after adjusting for BMI.ConclusionCDH13 polymorphisms are associated with prevalent T2D in this French population study. The association may be mediated through effects on BMI and/or plasma adiponectin.     

Association of the FTO gene with obesity and the metabolic syndrome is independent of the IRS-2 gene in the female population of Southern France

AimThe objective of the present study was to investigate the genetic association of the fat-mass-and-obesity-associated (FTO) gene in obese women in the presence of the known influential role of the insulin receptor substrate 2 (IRS-2) gene.MethodsThis case-control study was carried out in the Languedoc-Roussillon region of France, and included lean control women (n = 128), and women (n = 119) of various degrees of obesity (body mass index [BMI] mean ± S.D.: 39.3 ± 7.4 kg/m²) and a prevalence of 26.9% of the metabolic syndrome (MetS). For the FTO gene, genotyping was performed by sequence-specific oligonucleotide–polymerase chain reaction (SSO–PCR) on the single nucleotide polymorphism (SNP) rs1421085 (C/T) while, for IRS-2, the rs1805097 (G/A) corresponding to variant Gly1057Asp was genotyped by direct sequencing.ResultsThe FTO gene (homozygous C/C) was significantly associated to both simple and morbid obesity (P < 0.026 and P < 0.0034, respectively), with odds-ratios (ORs) of 2.58 (95% CI: 1.1–6.0) and 4.1 (95% CI: 1.6–10.5), respectively, independent of IRS-2. MetS was also associated with FTO (P < 0.032, OR: 3.1, 95% CI: 1.1–8.5), but not with IRS-2. Genotypes of FTO were correlated with insulin resistance, and homozygous C/C was positively correlated with an increase in insulin resistance over the value predicted by the increase in BMI.ConclusionThese data confirm the influential role of the FTO gene in obesity in the French female population and, in addition, revealed the role of FTO in insulin resistance and MetS. These effects appeared to be independent of IRS-2, which is directly involved in insulin action. This study may offer new insights into the genetic determinants of obesity and MetS in women.     

Influence of the CYP2J2 Gene Polymorphisms on Chronic Obstructive Pulmonary Disease Risk in the Chinese Han Population

IntroductionCytochrome P450 (CYP) 2J2 is a major enzyme that controls epoxyeicosatrienoic acids biosynthesis, which may play a role in chronic obstructive pulmonary disease (COPD) development. In this study, we aimed to assess the influence of CYP2J2 polymorphisms with COPD susceptibility.Material and methodsA case–control study enrolled 313 COPD cases and 508 controls was to investigate the association between CYP2J2 polymorphisms and COPD risk. Agena MassARRAY platform was used to genotype CYP2J2 polymorphisms. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the association between CYP2J2 polymorphisms and COPD risk.ResultsWe observed rs11207535 (homozygote: OR = 0.08, 95%CI = 0.01–0.96, p = 0.047; recessive: OR = 0.08, 95%CI = 0.01–0.94, p = 0.044), rs10889159 (homozygote: OR = 0.08, 95%CI = 0.01–0.92, p = 0.043; recessive: OR = 0.08, 95%CI = 0.01–0.90, p = 0.040) and rs1155002 (heterozygote: OR = 1.63, 95%CI = 1.13–2.36, p = 0.009; dominant: OR = 1.64, 95%CI = 1.15–2.35, p = 0.006; additive: OR = 1.45, 95%CI = 1.09–1.92, p = 0.011) were significantly associated with COPD risk. Allelic tests showed T allele of rs2280274 was related to a decreased risk of COPD and T allele of rs1155002 was associated with an increased COPD risk. Stratified analyses indicated the effects of CYP2J2 polymorphisms and COPD risk were dependent on gender and smoking status (p < 0.05). Additionally, two haplotypes (A_rs11207535C_rs10889159T_rs1155002 and A_rs11207535C_rs10889159C_rs1155002) significantly decreased COPD risk.ConclusionIt suggested CYP2J2 polymorphisms were associated with COPD susceptibility in the Chinese Han population.     

Polymorphisms of MMP-2 Gene are Associated With Systolic Heart Failure Risk in Han Chinese

BackgroundMatrix metalloproteinases (MMPs) are a family of proteolytic enzymes responsible for protein degradation. MMP-2 has been demonstrated to play a pivotal role in myocardial remodeling process that occurs in congestive heart failure (HF). We hypothesized that MMP-2 genetic variations could be associated with systolic HF risk.MethodsTo test the association of single nucleotide polymorphisms of MMP-2 with systolic HF risk, we performed a hospital-based, case-control study of 605 patients with systolic HF and 689 controls without HF. Three single nucleotide polymorphisms of MMP-2 (rs243864, rs243866, and rs17859821) were genotyped by restriction fragment length polymorphism methods.ResultsThe genotype frequencies of MMP-2 rs243866 AA and AG in the control group were significantly higher than that in the case group (24.7% versus 17.9%, P < 0.01). Compared with the GG homozygotes, MMP-2 rs243866 A allele carriers had a significantly lower risk of systolic HF (adjusted OR 0.69, 95% CI 0.49-0.98; P = 0.035). Haplotype analysis indicated the haplotype GGG (rs243864-rs17859821-rs243866) was associated with higher risk of systolic HF (adjusted OR 2.05, 95% CI 1.08-3.89; P = 0.028).ConclusionThe findings of the current study suggest that MMP-2 rs243866 A allele was associated with lower risk of systolic HF in Han Chinese.     

Relación entre la expresión de IL-2 e IL-4 y sus polimorfismos y los riesgos de padecer infección por Mycoplasma pneumoniae y asma en niños

IntroductionAsthma is an inflammatory disorder of the airways and the symptoms of asthma could be exacerbated by Mycoplasma pneumoniae infection. Interleukin-2 and interleukin-4 have been implicated in immune and inflammatory reactions. We examined the associations of IL2 and IL4 polymorphisms and expression with the risks of asthma and M. pneumoniae infection in children.Methods392 asthmatic children and 849 controls were recruited into the study. Eight polymorphisms in IL2 and IL4 were genotyped with Sequenom MassARRAY platform. M. pneumoniae infection and copy number was determined with fluorescence PCR. IL-2 and IL-4 serum expression levels were determined by using ELISA.ResultsWe found a significant association of IL2 rs6534349 polymorphism with increased asthma risk (heterozygotes, P = .029; homozygous variants; P = .013) and of IL4 rs2227284 polymorphism with reduced asthma risk (heterozygotes, P = .026; homozygous variants; P = .001). Besides, the association of other polymorphisms, except rs2070874 polymorphism, became apparent when the asthmatic children were grouped according to GINA classification of asthma control and severity. In addition, IL-2 and IL-4 serum expression levels were significantly higher in M. pneumoniae negative (P = .038) and positive (P = .011) subjects respectively. This observation holds true among asthmatic patients (P = .016 for IL-2 and P = .042 for IL-4), but only the IL-4 observation remained correct among non-asthmatic controls (P = .032). We also observed that the rs6534349 GG genotype was significantly associated with increased odds of getting high load M. pneumoniae infection (P = .0376).ConclusionsIL2 and IL4 could be important biomarkers for estimating the risks of asthma and M. pneumoniae infection in children.     

Long Non-coding RNA LINC-PINT and LINC00599 Polymorphisms are Associated With High-altitude Pulmonary Edema in Chinese

BackgroundHigh-altitude pulmonary edema (HAPE) is a kind of non-cardiogenic edema with high incidence and life-threatening. This study was designed to explore the association of LINC-PINT and LINC00599 polymorphisms with HAPE susceptibility.MethodsThis study included 244 HAPE patients and 243 age-, sex-matched healthy controls from the Chinese population. The genotypes of polymorphisms were detected using the Agena MassARRAY. The relationship between polymorphisms and HAPE risk was evaluated using a χ² test with an odds ratio (OR) and 95% confidence intervals (CIs) in multiple genetic models.ResultsWe observe a significant association between the rs157928 and decreased HAPE risk in genotype model (OR = 0.65, 95% CI = 0.43–0.98, p = 0.038). The subgroup analysis results indicated that rs2272026 was associated with a decreased risk of HAPE in younger patients with age ≤32 (codominant model: p = 0.006; recessive model: p = 0.005 additive model: p = 0.018; and allele model: p = 0.012; rs72625676, codominant model: p = 0.038; recessive model: p = 0.037). Among patients older than 32 years, there was a significantly increased risk of HAPE associated with the rs2272026 and rs1962430 (rs2272026: genotype model: p = 0.049; recessive model: p = 0.029; rs1962430: genotype model: p = 0.024; recessive model: p = 0.020). Nevertheless, rs157928 had relationship with significantly reducing the risk of HAPE in the genotype model (p = 0.018).ConclusionOur study suggests that LINC-PINT and LINC00599 polymorphisms are associated with HAPE susceptibility in Chinese population.     

Hematological parameters and metabolic syndrome: Findings from an occupational cohort in Ethiopia

AimsTo examine associations between hematological parameters (i.e., hemoglobin, hematocrit, platelet counts, red blood cell (RBC), and white blood cell (WBC) counts) and components of metabolic syndrome (MetS) among working adults in Addis Ababa, Ethiopia.Materials and MethodsParticipants were 1868 (1131 men and 737 women) working Ethiopian adults. MetS was classified according to the International Diabetes Federation criterion. Odds ratios (ORs) and 95% confidence intervals (95% CIs) of MetS were calculated using logistic regression procedures.ResultsHematologic parameters (hemoglobin, hematocrit, and RBC) were positively associated with MetS components (P_trend < 0.05). In both men and women, white blood cell (WBC) counts were positively associated with BMI and waist circumference (P < 0.05). RBC counts were associated with diastolic blood pressure in men (P < 0.05) and women (P < 0.001). Men in the third quartile of hemoglobin concentrations had 2-fold increased odds (OR = 1.99; 95% CI) of MetS compared with the lowest reference quartile (P_trend = 0.031) while women in the fourth hemoglobin quartile had 2.37-fold increased odds of having MetS compared with the reference group (P_trend = 0.003). Both men and women in the fourth quartiles of RBC counts had 2.26-fold and 3.44-fold increased odds of MetS (P = 0.002 in men, P < 0.001 in women). Among women, those in the fourth quartiles of hematocrit and platelet counts had 2.53-fold and 2.01-fold increased odds of MetS as compared with those in the reference group (P_trend = 0.004 and 0.065 respectively).ConclusionOur study findings provide evidence in support of using hematological markers for early detection of individuals at risk for cardiovascular disease.     

Predictors of insulin resistance in the obese with metabolic syndrome

BackgroundIn the obese, the metabolic syndrome (MetS) is assumed to reflect insulin resistance.ObjectiveTo determine the predictors of insulin resistance in obese subjects with MetS.DesignWe used the 90th percentile of the homeostasis model assessment (HOMA) to define insulin resistance in 4958 nondiabetic adults evaluated in the National Health and Nutrition Examination Surveys, 1999–2004, and compared the 373 obese subjects who were insulin-resistant (HOMA 9.52 ± 5.73) to a control group of 373 obese who had the highest sensitivity to insulin (HOMA 1.79 ± 0.44).MeasurementsMetS was present in 312 (83.6%) obese with insulin resistance and in 156 (41.8%) obese from the insulin-sensitive control group. Demographic, metabolic, and lifestyle variables were analyzed with logistic regression.ResultsIn a logistic model of insulin resistance given the presence of MetS, the significant predictors were triglycerides (P = 0.0021), body mass index (P = 0.0096), HDL-cholesterol (P = 0.0098), age (P = 0.0242) and smoking (P = 0.0366).LimitationsCross-sectional design prevents elucidation of causality for the association between insulin resistance and MetS.ConclusionsInsulin resistance is not an obligatory correlate of MetS in the obese. Its likelihood can be predicted by cigarette smoking and by the severity of obesity and dyslipidemia.     

Renin angiotensin system polymorphisms in patients with metabolic syndrome (MetS)

BackgroundThe genes associated with hypertension could be genetic risk factors for metabolic syndrome (MetS).AimTo determine the frequency of M235T and T174M-AGT, I/D-ACE and A1166C-AGTR1 in hypertensive patients with MetS and to evaluate the relationship between these polymorphisms and central obesity and dyslipidemia, respectively.Materials and methodsWe performed AGT, AGTR1 and ACE genotyping in 56 hypertensive women (24 with MetS) and 71 normotensive women using PCR-RFLP methods and PCR, respectively.ResultsHypertensive patients carrying the mutated TT235, MM174 and DD genotypes had an 1.53 (p = 0.56), 1.78 (p = 0.52) and 1.28 (p = 0.78)-fold increased risk to develop MetS. Hypertensive carriers of both mutated TT235 and MM174 or TT235 and D/D or TT235 and CC + AC genotypes had an 8.15 (p = 0.04), 4.83 (p = 0.04) and 10.53 (p = 0.05)-fold increased risk to develop MetS. Hypertensive patients with MetS and TT, D/D or CC genotypes had higher body mass index compared to hypertensive patients without MetS (p ≤ 0.05 for all the genotypes). Hypertensive patients with MetS and TT235, MM174, D/D or CC1166 genotypes had higher triglyceride levels, lower HDL-cholesterol levels and higher waist circumference compared to hypertensive patients without MetS (p ≤ 0.05, except for the association between CC1166 and HDL-cholesterol level).ConclusionsThe effect of the T174M, I/D and A1166C polymorphisms on MetS may depend on the M235T polymorphism. Among hypertensive subjects with MetS, the presence of TT235, MM174, DD and CC1166 genotypes could be a risk factor for central obesity and dyslipidemia.     

Lack of replication of common EXT2 gene variants with susceptibility to type 2 diabetes in Lebanese Arabs

ObjectiveRecent genome-wide association studies and replication analyses have reported the association of variants of the exostosin-2 (EXT2) gene and risk of type 2 diabetes mellitus (T2DM) in some populations, but not in others. This study investigated the associations of EXT2 variants rs1113132, rs3740878 and rs11037909 with T2DM in a Lebanese Arab population.MethodsThis case-control study involved 995 T2DM patients and 1076 control subjects. Genotyping was done by the allelic exclusion method.ResultsWhile minor allele frequencies (MAFs) of rs11037909 (P = 0.028) and rs3740878 (P = 0.048), but not rs1113132 (P = 0.841), were higher in patients, this was lost after correcting for multiple testing. Apart from EXT2 rs1113132, which was marginally associated with T2DM in the additive model (P = 0.054), but not after adjustment for covariates, none of the tested EXT2 SNPs were associated with T2DM in any of the genetic models tested. However, variable associations of EXT2 variants with T2DM were noted according to BMI status. While the three tested EXT2 variants were not associated with T2DM in obese subjects, rs1113132 and rs11037909, but not rs3740878, were associated with T2DM in non-obese subjects. Meta-analysis revealed a significant association of rs11037909 and a marginal association of rs3740878 with T2DM in the fixed model. Using a common (GTA) haplotype as reference, three-locus (rs1113132/rs11037909/rs3740878) haplotype analysis demonstrated no association between any of the EXT2 haplotypes with T2DM, not even before correcting for multiple testing.ConclusionThis study demonstrated no association of rs1113132, rs3740878 and rs11037909 EXT2 variants with T2DM.     

Influence of apolipoprotein E gene polymorphism on development of type 2 diabetes mellitus in Chinese Han population: A meta-analysis of 29 studies

ObjectivesPublished data regarding the association between apolipoprotein E (ApoE) gene polymorphism and type 2 diabetes mellitus (T2DM) risk in Chinese Han population were inconclusive. To derive a more precise estimation of the relationship between this variant and T2DM risk in Chinese Han population, we performed this meta-analysis.Design and methodsA computerized literature search was conducted to identify the relevant studies from PubMed, EMbase, Web of Science, CBMdisc, CNKI, and Google Scholar. Additionally, hand searching of the references of identified articles was performed. All the statistical tests were performed using Stata 11.0.ResultsA total of 29 articles with 4615 T2DM cases and 2867 controls were included in the present meta-analysis. The results showed evidence for significant association between ApoE gene polymorphism and T2DM risk (for ε2/ε3 vs. ε3/ε3: OR = 1.37, 95% CI = 1.12–1.68, P < 0.01; for ε3/ε4 vs. ε3/ε3: OR = 1.53, 95% CI = 1.23–1.91, P < 0.01; for ε4/ε4 vs. ε3/ε3: OR = 1.86, 95% CI = 1.22–2.84, P < 0.01; for ε2 allele vs. ε3 allele: OR = 1.28, 95% CI = 1.08–1.52, P = 0.01; for ε4 allele vs. ε3 allele: OR = 1.43, 95% CI = 1.22–1.68, P < 0.01). In addition, significant association was also found between ApoE gene polymorphism and diabetic nephropathy (DN) risk.ConclusionsThe results of this meta-analysis suggest that the ApoE ε2 and ε4 alleles may be associated with increased risks of T2DM and DN in Chinese Han population. Additional well-designed genome-wide association studies are required to confirm these results.     

TNFSF15 is an independent predictor for the development of Crohn's disease-related complications in Koreans

BackgroundCrohn's disease (CD) is a chronic idiopathic inflammatory bowel disease involving the whole gastrointestinal tract. TNFSF15 has been proved as a susceptibility gene for CD, but there are few reports about the association between TNFSF15 single nucleotide polymorphisms (SNPs) and the clinical course of CD.AimTo investigate the association between TNFSF15 genotypes and the clinical course of CD in Koreans.MethodsA total of 906 CD patients having TNFSF15 genotype data and clinical information were recruited from CD registry database of a tertiary referral center. The association between five TNFSF15 SNPs (rs4574921, rs3810936, rs6478108, rs6478109, and rs7848647) and various clinical parameters including stricture, non-perianal penetrating complications, bowel resection, and reoperation was investigated.ResultsAmong the five SNPs, rs6478108 CC genotype was associated with the development of stricture and non-perianal penetrating complications during follow-up (HR for stricture = 1.706, 95% confidence interval 1.178–2.471, P = 0.005; HR for non-perianal penetrating complications = 1.667, 95% confidence interval 1.127–2.466, P = 0.010), and rs4574921 CC genotype was associated with the development of perianal fistula (HR = 2.386, 95% confidence interval 1.204–4.727, P = 0.013) by multivariate analysis. However, there was no significant association of cumulative operation and reoperation rate with 5 SNPs of TNFSF15.ConclusionIn Korean patients with CD, non-risk allele homozygotes of TNFSF15 SNPs rs6478108 and rs4574921 are independent genetic predictive factors for the development of strictures/non-perianal penetrating complications and perianal fistula, respectively.     

Reduced risk of metabolic syndrome due to regular intake of vegetables rich in antioxidants among African type 2 diabetics

BackgroundAntioxidant nutrients found in vegetables are thought to prevent chronic diseases including type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS).ObjectiveWe evaluated the prevalence of MetS and the association of antioxidants and cardiovascular risk factors with risk of MetS among patients with T2DM from General hospital of Kinshasa, DRC.MethodsThis cross-sectional study using a validated semiquantitative food frequency questionnaire. MetS was defined using criteria of IDF/Europids, IDF modified for Africa and NCEP-ATP III. Risk factors of MetS (OR and 95% CI) was estimated using logistic regression, adjusting for confounding factors.ResultsOut of 244 T2 DM patients (56.6% of females) and 48 ± 16 years, 0%, 13%, 34.4%, 20.9%, and 11.9% were defined by never consuming fruits, never consuming vegetables, MetS/IDF Europids, MetS/IDF modified for Africa, and MetS/NCEP-ATP III. Females (OR = 5 95% CI 2–10; P < 0.01), High socioeconomic status (HSES, OR = 3.5, 95% CI 1.5–8.3; P = 0.005), and regular Cassava leaves intake (OR= 0.4, 95% CI 0.2–0.9; P = 0.027) were the independent determinants of MetS/IDF Europids. HSES (OR= 2.9, 95% CI 1.2–6.9; P = 0.015), physical inactivity (OR = 2.6, 95% CI 1.6–6; P = 0.03) and regular dry red beans intake (OR = 0.4, 95% CI 0.2–0.8; P = 0.016) were the independent determinants of MetS/IDF modified for Africa. Females (OR = 5, 95% CI 2–20; P < 0.001), HSES (OR = 3.5, 95% CI 1.5–8.3; P = 0.005) and regular Cassava leaves intake (OR = 0.4, 95% CI 0.2–0.9; P < 0.0001) were the independent determinants of MetS/NCEP-ATP III.ConclusionCassava leaves and dried red beans intake, rich in antioxidants, are protective factors against MetS presence, while females, HSES, and physical inactivity are independent risk factors of MetS.     

Associations between a fetal imprinted gene allele score and late pregnancy maternal glucose concentrations

AimWe hypothesised that some of the genetic risk for gestational diabetes (GDM) is due to the fetal genome affecting maternal glucose concentrations. Previously, we found associations between fetal IGF2 gene variants and maternal glucose concentrations in late pregnancy.MethodsIn the present study, we tested associations between SNP alleles from 15 fetal imprinted genes and maternal glucose concentrations in late pregnancy in the Cambridge Baby Growth and Wellbeing cohorts (1160 DNA trios).ResultsFour fetal SNP alleles with the strongest univariate associations: paternally-transmitted IGF2 rs10770125 (P-value = 2 × 10^–4) and INS rs2585 (P-value = 7 × 10^–4), and maternally-transmitted KCNQ1(OT1) rs231841 (P-value = 1 × 10^–3) and KCNQ1(OT1) rs7929804 (P-value = 4 × 10^–3), were used to construct a composite fetal imprinted gene allele score which was associated with maternal glucose concentrations (P-value = 4.3 × 10^–6, n = 981, r² = 2.0%) and GDM prevalence (odds ratio per allele 1.44 (1.15, 1.80), P-value = 1 × 10^–3, n = 89 cases and 899 controls). Meta-analysis of the associations including data from 1367 Hyperglycaemia and Adverse Pregnancy Outcome Study participants confirmed the paternally-transmitted fetal IGF2/INS SNP associations (rs10770125, P-value = 3.2 × 10^–8, rs2585, P-value = 3.6 × 10^–5) and the composite fetal imprinted gene allele score association (P-value = 1.3 × 10^–8), but not the maternally-transmitted fetal KCNQ1(OT1) associations (rs231841, P-value = 0.4; rs7929804, P-value = 0.2).ConclusionThis study suggests that polymorphic variation in fetal imprinted genes, particularly in the IGF2/INS region, contribute a small but significant part to the risk of raised late pregnancy maternal glucose concentrations.     

Prevalencia de variantes de alto riesgo de alfa-1 antitripsina en población mestiza mexicana y su relación con los valores de la función pulmonar

IntroductionChronic obstructive pulmonary disease (COPD) is characterized by restricted airflow. The best-documented genetic factor is alpha-1 antitrypsin (AAT). AAT is encoded by the SERPINA1 gene. The PiZ (rs28929474) and PiS (rs17580) variants are believed to cause severe AAT deficiency and are linked to a high risk of developing COPD. This study sought to identify whether genetic polymorphisms rs28929474 and rs17580 are associated with COPD susceptibility and lung function values in a Mexican mestizo population.MethodsIn this study, 558 smokers were included, of whom 279 had COPD and 279 did not (smokers without COPD - SWC). The PiS and PiZ variants were genotyped by allelic discrimination. Independent populations and lung function values were compared using the Kruskal-Wallis test. A bivariate logistic regression analysis was also conducted.ResultsStage I and iv COPD patients showed significant differences in the frequencies of both heterozygous genotypes compared to SWC. For PiS, individuals with the heterozygous genotype AT demonstrated a decreased FEV1/FVC ratio compared to subjects with the homozygous genotype AA (P = 0.037). A significant association was found between the FEV1/FVC ratio and genotype AA for PiS (OR = 0.982, β coefficient = –0.019, 95% CI = 0.966-0.997).ConclusionsCOPD-causing AAT deficiency risk alleles exist at a very low frequency among Mexican mestizo population. Although they are not directly linked in our study population with disease susceptibility, these risk alleles are associated with poorer lung function measurements. It is important to characterize how often these genetic risk variants occur in other Latin American populations.     

Genetics of melatonin receptor type 2 is associated with left ventricular function in hypertensive patients treated according to guidelines

BackgroundMelatonin exerts multiple biological effects with potential impact on human diseases. This is underscored by genetic studies that demonstrated associations between melatonin receptor type 2 gene (MTNR1B) polymorphisms and characteristics of type 2 diabetes. We set out to test the hypothesis whether genetic variants at MTNR1B are also relevant for other disease phenotypes within the cardiovascular continuum. We thus investigated single nucleotide polymorphisms (SNPs) of MTNR1B in relation to blood pressure (BP) and cardiac parameters in hypertensive patients.MethodsPatients (n = 605, mean age 56.2 ± 9.4 years, 82.3% male) with arterial hypertension and cardiac ejection fraction (EF) ≥ 40% were studied. Cardiac parameters were assessed by echocardiography.ResultsThe cohort comprised subjects with coronary heart disease (73.1%) and myocardial infarction (48.1%) with a mean EF of 63.7 ± 8.9%. Analysis of SNPs rs10830962, rs4753426, rs12804291, rs10830963, and rs3781638 revealed two haplotypes 1 and 2 with frequencies of 0.402 and 0.277, respectively. Carriers with haplotype 1 (CTCCC) showed compared to non-carriers a higher mean 24-hour systolic BP (difference BP: 2.4 mm Hg, 95% confidence interval (CI): 0.3 to 4.5 mm Hg, p = 0.023). Haplotype 2 (GCCGA) was significantly related to EF with an absolute increase of 1.8% (CI: 0.45 to 3.14%) in carriers versus non-carriers (p = 0.009).ConclusionGenetics of MTNR1B point to impact of the melatonin signalling pathway for BP and left ventricular function. This may support the importance of the melatonin system as a potential therapeutic target.