Interaction between vitamin D receptor gene polymorphisms and 25-hydroxyvitamin D concentrations on metabolic and cardiovascular disease outcomes

Aim25-hydroxyvitamin D (25OHD) concentrations have been shown to be associated with major clinical outcomes, with a suggestion that individual risk may vary according to common genetic differences in the vitamin D receptor (VDR) gene. Hence, we tested for the interactions between two previously studied VDR polymorphisms and 25OHD on metabolic and cardiovascular disease-related outcomes in a large population-based study.MethodsInteractions between two previously studied VDR polymorphisms (rs7968585 and rs2239179) and 25OHD concentrations on metabolic and cardiovascular disease-related outcomes such as obesity- (body mass index, waist circumference, waist-hip ratio (WHR)), cardiovascular- (systolic and diastolic blood pressure), lipid- (high- and low-density lipoprotein, triglycerides, total cholesterol), inflammatory- (C-reactive protein, fibrinogen, insulin growth factor-1, tissue plasminogen activator) and diabetes- (glycated haemoglobin) related markers were examined in the 1958 British Birth cohort (n up to 5160). Interactions between each SNP and 25OHD concentrations were assessed using linear regression and the likelihood ratio test.ResultsAfter Bonferroni correction, none of the interactions reached statistical significance except for the interaction between the VDR SNP rs2239179 and 25OHD concentrations on waist-hip ratio (WHR) (P = 0.03). For every 1 nmol/L higher 25OHD concentrations, the association with WHR was stronger among those with two major alleles (−4.0%, P = 6.26e⁻²⁴) compared to those with either one or no major alleles (−2.3%, P ≤ 8.201e⁻⁰⁷, for both) of the VDR SNP rs2239179.ConclusionWe found no evidence for VDR polymorphisms acting as major modifiers of the association between 25OHD concentrations and cardio-metabolic risk. Interaction between VDR SNP rs2239179 and 25OHD on WHR warrants further confirmation.     

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.     

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.     

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.     

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.     

Genetic variation at chromosome 1p13.3 affects sortilin mRNA expression,cellular LDL-uptake and serum LDL levels which translates to the risk of coronary artery disease

BackgroundA single nucleotide polymorphism (SNP) rs599839 located at chromosome 1p13.3 has previously been associated with risk of coronary artery disease (CAD) and with serum levels of low-density lipoprotein cholesterol (LDL-C). A functional link explaining the association of SNP rs599839 with LDL-C levels and CAD risk has not yet been elucidated.MethodsWe analyzed the association of rs599839 with LDL-C in 6605 individuals across a wide age spectrum and with CAD in four case–control studies comprising 4287 cases and 7572 controls. Genome-wide expression array data was used to assess the association of SNP rs599839 with gene expression at chromosome 1p13. Finally, we overexpressed sortilin in transfected cells to study LDL-uptake in vitro.ResultsEach copy of the G-allele of rs599839 associated with a decrease of serum LDL-C by 0.14 mmol/L (90% confidence interval (CI) 0.09–0.17 mmol/L, p = 2.6 × 10^?11). Moreover, each copy of the G-allele associated with a 9% decrease of CAD risk (90% CI 4–14%) in the presently studied four case–control samples and with a 13% decrease (90% CI 10–17%, p = 2.18 × 10^?9) in a pooled meta-analysis including recent genome-wide association studies on CAD. The same allele was associated with higher mRNA-expression levels of the multiligand receptor sortilin (log transformed mRNA AA vs. GG = 8.31 vs. 8.55; p = 0.01). Overexpression of SORT1 cDNA resulted in a significant increase in LDL-particle uptake (+23%, p = 0.01).ConclusionsRs599839 associates with decreased LDL-C and a lower risk of CAD. Effects appear to be mediated by increased sortilin expression and subsequently enhanced LDL-uptake into cells.     

The APOE ɛ2 allele is associated with increased plasma apolipoprotein E levels in patients with coronary artery disease

AimsWe sought to evaluate the influence of APOE polymorphisms (ɛ2-rs7412, ɛ4-rs429358) on plasma levels of apolipoprotein E in patients with confirmed coronary artery disease.MethodsA total of 94 patients with coronary artery disease were included in our study. Genotypisation for rs429358 and rs7412 in APOE was performed and plasma levels of apolipoprotein E, lipids, and hs-CRP were measured.ResultsSignificantly higher plasma levels of APOE were found in the ɛ2 carriers compared to the normal ɛ3/ɛ3 genotype (40.4 mg/mL vs. 22.9 mg/mL, P = 0.018). There was no difference in APOE levels between the ɛ4 allele and ɛ3/ɛ3 allele carriers. Significantly higher HDL cholesterol levels (1.55 mmol/L vs. 1.16 mmol/L, P = 0.001) were found in the ɛ2 carriers, and significantly lower levels of hs-CRP (1.07 mg/L vs. 2.14 mg/L, P = 0.035) in the ɛ4 carriers compared to the normal ɛ3/ɛ3 genotype.ConclusionsIn CAD patients, the ɛ2 APOE allele is associated with significantly higher plasma levels of APOE and HDL cholesterol, whereas the ɛ4 allele is associated with significantly lower levels of hsCRP.     

The impact of angiotensin converting enzyme insertion/deletion gene polymorphism on diabetic kidney disease: A debatable issue

ObjectiveThe objective of this study was to evaluate the influence of ACE I/D gene polymorphisms on diabetic kidney disease (DKD) risk.MethodsAll eligible investigations were identified, the number of various genotype in the case and control group were reviewed. The pooled analysis was performed using Stata software.ResultsIn overall subjects, 24,321 participants with 12,961 cases and 11,360 controls were included. the pooled analysis showed a significant link between D allele, DD or II genotype and DKD risk (D versus I: OR = 1.316, 95% CI: 1.213–1.427, P = 0.000; DD versus ID + II: OR = 1.414, 95% CI: 1.253–1.595, P = 0.000; II versus DD + ID: OR = 0.750, 95% CI: 0.647–0.869, P = 0.000). The subgroup pooled analysis showed that ACE I/D gene polymorphism was correlated with DKD both in Asian and in Chinese population. In addition, ACE I/D gene polymorphism was correlated with type 2 DKD (D versus I: OR = 1.361, 95% CI: 1.243–1.490, P = 0.000; DD versus ID + II: OR = 1.503, 95% CI: 1.310–1.726, P = 0.000; II versus DD + ID: OR = 0.738, 95% CI: 0.626 –0.870, P = 0.000). However, there was no obvious correlation in Caucasian subjects and type 1 diabetic patients.ConclusionACE I/D polymorphisms were correlated with DKD in Asian and type 2 diabetic populations. ACE D allele/DD genotype might be a risk factor, while ACE II genotype might be a protective factor for DKD.     

Clinical profile and impact of family history of premature coronary artery disease on clinical outcomes of patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction: analysis from the HORIZONS-AMI Trial

Background/PurposeFamily history of coronary artery disease (CAD) is a well-established risk factor of future cardiovascular events. The authors sought to examine the relationship between family history of CAD and clinical profile and prognosis of patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).Materials/MethodsBaseline features and clinical outcomes at 30 days and at 3 years from 3601 patients with STEMI enrolled in the HORIZONS-AMI trial were compared in patients with and without family history of premature CAD, which was present in 1059 patients (29.4%).ResultsThese patients were younger (median 56.7 vs. 62.1 years, P < 0.0001) and more often current smokers (52.4% vs. 43.5%, P < 0.0001), had more dyslipidemia (47.7% vs. 41.1%, P = 0.0003), less diabetes mellitus (14.1% vs. 17.5%, P = 0.01) and had shorter symptom onset to balloon times (median 213 vs. 225 min, P = 0.02). Patients with a family history of premature CAD had higher rates of final TIMI 3 flow (93.8% vs. 90.6%, P = 0.002), and myocardial blush grade 2 or 3 (83.2% vs. 78.0% P = 0.0008), and fewer procedural complications. Although the unadjusted 30-day and 3-year mortality rates were lower in patients with a family history of premature CAD (1.8% vs. 3.0%, P = 0.046 and 4.8% vs. 7.7%, P = 0.002, respectively), by multivariable analysis the presence of a family history of premature CAD was not an independent predictor of death at 3 years (HR [95%CI] = 1.00 [0.70, 1.44], P = 0.98).ConclusionsA family history of premature CAD is not an independent predictor of higher mortality.     

Association of the six transmembrane protein of prostate 2 gene polymorphisms with metabolic syndrome in Han Chinese population

AimThe six-transmembrane protein of prostate 2 (STAMP2) has been demonstrated to play a potential role in the pathogenesis of metabolic syndrome (MetS). The present study was designed to investigate the association of STAMP2 gene polymorphisms with MetS in Han Chinese population.MethodsA case-control study enrolled 350 Han Chinese subjects in two groups: 182 MetS patients and 168 control subjects. The clinical and biochemical characteristics were determined. Three single nucleotide polymorphisms (SNPs), rs1981529, rs12386756 and rs10263111 in STAMP2 gene were genotyped. The association of STAMP2 gene polymorphisms with MetS was analyzed.ResultsSNPs rs1981529 and rs10263111 were found to be significantly associated with MetS phenotype in male population (P = 0.014 and 0.025). Moreover, SNP rs1981529 was found to be associated with high density lipoprotein-cholesterol in male cases and with body mass index in female cases (P = 0.014 and 0.049). SNP rs10263111 was found to be associated with both waist circumference and diastolic blood pressure in total cases (P = 0.044 and 0.033). Haplotype analysis yielded significant association of STAMP2 gene with MetS in total (global P = 0.0109) and male population (global P = 0.0004).ConclusionOur findings revealed that STAMP2 gene polymorphisms are likely to significantly contribute to the risk of MetS in male Han Chinese population.     

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.     

Relationship of apolipoprotein E polymorphism with lipid profiles in atherosclerotic coronary artery disease

AimsThe aim was to determine the relationship between apolipoprotein E (ApoE) gene polymorphisms and lipid profile in patients with coronary artery diseases (CAD), and its role in the prediction of the severity of carotid and coronary atherosclerosis.Methods and resultsOne hundred patients were classified by coronary angiography: 80 patients with CAD and 20 controls (normal coronary angiography). Clinical data, carotid sonography, blood lipid profiles and ApoE genotyping (PCR-RFLP) were assessed. CAD patients had significantly increased plasma lipid profiles and carotid intimal-wall thickness (IMT) versus controls. In CAD patients; ApoE genotype frequencies were E3/E3 = 62.50%, E2/E3 = 18.75%, E3/E4 = 17.50%, E2/E4 = 1.25%, E4/E4 = 0 and E2/E2 = 0. But, E3/E4 genotype was significantly higher than controls (P < 0.05). Also, in CAD patients; ApoE allele frequencies were E3 = 80.6%, E2 = 10.0% and E4 = 9.4% but, ApoE4 alleles were associated with higher cholesterol (P = 0.034) and LDL-c (P = 0.003), while ApoE2 alleles were associated with higher triglycerides (P = 0.037) versus ApoE3 alleles. However, odds ratio of CAD patients had higher risk with E2/E3 genotypes (2.5-fold), E2 alleles (2.2-fold) and E4 alleles (2.1-fold). Moreover, CAD patients with ApoE4 alleles had significantly higher carotid IMT (1.23 ± 0.26 mm vs 0.97 ± 0.2 mm ApoE3, P = 0.006; however, non-significant vs 1.10 ± 0.40 mm ApoE2 and also, ApoE2 vs ApoE3 alleles, P = 0.633) and left anterior descending (LAD) coronary artery stenosis (vs ApoE3 alleles, P = 0.016).ConclusionIschemic patients with carotid and coronary atherosclerosis had significantly higher integration of dyslipidemia and ApoE alleles (ApoE2 with hypertriglyceridemia and ApoE4 with hypercholesterolemia and higher LDL-c). ApoE polymorphism may be an important diagnostic risk biomarker and may implicate therapeutic intervention in atherosclerotic ischemic patients.     

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.     

Haplotypes and 5A/6A polymorphism of the matrix metalloproteinase-3 gene in coronary disease: Case–control study and a meta-analysis

ObjectiveMatrix metalloproteinase-3 and its gene, MMP3, have been implicated in atherosclerotic diseases of coronary arteries. We conducted a haplotype analysis to examine the role of common variation of MMP3 in myocardial infarction (MI) and a meta-analysis to combine available evidence on the association between the 5A/6A polymorphism (rs3025058) and coronary diseases.Methods and resultsGenotype distributions of haplotype-tagging single nucleotide polymorphisms (rs522616, rs650108, rs569444, rs635746) and rs3025058 were not significantly different between a group with MI (n = 3657) and a control group (n = 1211) (p ≥ 0.24). Five major haplotypes were established, and their frequencies were not substantially different between the case and control groups (p ≥ 0.11). In a meta-analysis of 15 studies (10,061 cases, 8048 controls), the overall risk of coronary disease was not different between the carriers of the 5A allele and 6A6A genotype of rs3025058 (OR, 1.00; 95% CI, 0.85–1.19). Moderate trends of a reduced risk in the 5A allele carriers of European ancestry (OR, 0.87; 95% CI, 0.76–1.00) and an increased risk in the 5A allele carriers from East Asia (OR, 1.33; 95% CI, 0.94–1.90) were observed.ConclusionsIndividual polymorphisms and haplotypes of MMP3 were not associated with MI in a German case–control study. Evidence was obtained to suggest different risk effects of rs3025058 between Europeans and East Asians.     

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.     

Risk of coronary artery disease associated with initial sulphonylurea treatment of patients with type 2 diabetes: A matched case–control study

AimsThis study sought to assess the risk of developing coronary artery disease (CAD) associated with initial treatment of type 2 diabetes with different sulphonylureas.MethodsIn type 2 diabetic patients, cases who developed CAD were compared retrospectively with controls that did not. The 20-year risk of CAD at diagnosis of diabetes, using the UKPDS risk engine, was used to match cases with controls.ResultsThe 76 cases of CAD were compared with 152 controls. The hazard of developing CAD (95% CI) associated with initial treatment increased by 2.4-fold (1.3–4.3, P = 0.004) with glibenclamide; 2-fold (0.9–4.6, P = 0.099) with glipizide; 2.9-fold (1.6–5.1, P = 0.000) with either, and was unchanged with metformin. The hazard decreased 0.3-fold (0.7–1.7, P = 0.385) with glimepiride, 0.4-fold (0.7–1.3, P = 0.192) with gliclazide, and 0.4-fold (0.7–1.1, P = 0.09) with either.ConclusionsInitiating treatment of type 2 diabetes with glibenclamide or glipizide is associated with increased risk of CAD in comparison to gliclazide or glimepiride. If confirmed, this may be important because most Indian patients receive the cheaper older sulphonylureas, and present guidelines do not distinguish between individual agents.     

Paraoxonase 1 gene (Gln192–Arg) polymorphism and the risk of coronary artery disease in type 2 diabetes mellitus

BackgroundParaoxonase 1 (PON1) is reported to have antioxidant and cardioprotective properties. Recently, an association of glutamine (Gln) or type A/arginine (Arg) or type B polymorphism at position 192 of PON1 gene has been suggested with coronary artery disease (CAD) among patients with diabetes mellitus (DM). However, conflicting results have also been reported.ObjectivesTo investigate the relationship between PON1 gene (Gln¹⁹²–Arg) polymorphism and the presence, extent and severity of CAD in type 2 DM.MethodsThe study comprised 180 patients recruited from those undergoing coronary angiography for suspected CAD, who were divided according to the presence or absence of CAD and DM into four groups: Group I (n = 40 patients) nondiabetic subjects without CAD, Group II (n = 45 patients) diabetic patients without CAD, Group III (n = 47 patients) nondiabetic patients with CAD and Group IV (n = 48 patients) diabetic patients with CAD. PON1(Gln¹⁹²–Arg) genotype was assessed using polymerase chain reaction (PCR) followed by AlwI digestion.ResultsThe frequency of Gln allele (type A) was significantly higher in Group I and Group II compared to Group III and Group IV (62.5%, 60% vs. 38.3%, 31.25%, respectively, p < 0.001) while the frequency of Arg allele (type B + type AB) was significantly higher in ischemic groups (III and IV) compared to nonischemic groups (I and II) (61.7%, 68.75% vs. 37.5%, 40%, respectively, p < 0.001). Patients with CAD and DM (Group IV) have significantly higher severity score and vessel score than those with CAD only (Group III) (9.7 ± 2.97, 2.44 ± 0.56 vs. 6.99 ± 3.71, 1.67 ± 0.89, respectively, p < 0.001) Patients with vessel score 3 had significantly higher severity score and higher Arg allele frequency than patients with vessel score 2, the latter group had also significantly higher severity score and Arg allele frequency than patients with vessel score 1 (8.9 ± 2.79 vs. 5.21 ± 2.13 and 80.49% vs. 67.86%), (5.21 ± 2.13 vs. 3.11 ± 0.89 and 67.86% vs. 53.85%), p < 0.001 for all. In multivariate logistic regression analysis of different variables for prediction of CAD, age [OR 2.99, CI (1.11–10.5), p < 0.01], smoking [OR 4.13, CI (1.37–11.7), p < 0.001], low-density lipoprotein (LDL) cholesterol > 100 mg/dL [OR 4.31, CI (1.25–12.5), p < 0.001], high-density lipoprotein (HDL) cholesterol < 40 mg/dL [OR 5.11, CI (1.79–16.33), p < 0.001] and PON1 192 Arg allele [OR 4.62, CI (1.67–13.57), p < 0.001] were significantly independent predictors of CAD.ConclusionArg allele of PON1 192 gene polymorphism is an independent risk factor for CAD and is associated not only with the presence of CAD but also with its extent and severity and its impact is clearly more pronounced in diabetic patients.     

Polymorphisms of TGFB1, TLE4 and MUC22 are associated with childhood asthma in Chinese population

ObjectiveTo investigate whether the genetic variants of TGFB1, TLE4, MUC22 and IKZF3 are associated with the development of asthma in Chinese children.Methods572 adolescent asthma patients and 590 age-matched healthy controls were included in this study. A total of four SNPs were genotyped, including rs2241715 of TGFB1, rs2378383 of TLE4, rs2523924 of MUC22, and rs907092 of IKZF3. Allele frequencies of the patients and the control group were compared by the Chi-square test. The Student t test was used to analyse the relationship between genotypes and clinical feature of the patients.ResultsPatients were found to have significantly different frequencies of allele A of rs2241715, allele G of rs2378383 and allele A of rs2523924 as compared with the controls (40.4% vs. 45.9%, p = 0.01 for rs2241715; 17.2% vs. 13.4%, p = 0.01 for rs2378383; 15.3% vs. 11.9%, p = 0.02 for rs2523924). For patients with severe asthma, those with genotype AA/AG of rs2241715 had remarkably higher FEV1% as compared with those with genotype GG (59.1 ± 4.3% vs. 55.4 ± 3.7%, p < 0.001). Moreover, those with genotype GG/GA of rs2378383 had remarkably lower FEV1% as compared with those with genotype AA (54.6 ± 2.9% vs. 58.6 ± 4.1%, p < 0.001).ConclusionsGenes TGFB1, TLE4 and MUC22 are associated with the risk of childhood asthma in Chinese population. Our results associating TGFB1 and TLE4 with clinical features of asthma suggest potential application of these parameters in the management of asthma children.     

OCTN1 variant L503F is associated with familial and sporadic inflammatory bowel disease

PurposeA two-allele haplotype of TC (OCTN1 rs1050152 and OCTN2 -207G→C) is associated with Crohn's disease (CD). The association has been replicated in different populations, but also failed in some studies. The present study is to replicate the association of OCTN1 rs1050152 and examine another variant rs272879 with familial and sporadic inflammatory bowel disease (IBD) in a cohort from central Pennsylvania, USA.MethodsThe study samples (n = 465) included 212 inflammatory bowel disease patients (CD = 115, UC = 97), including 103 familial (CD = 55, UC = 46) and 111 sporadic (CD = 60, UC = 51) IBD, 139 non-IBD family members from a familial IBD registry, and 114 unrelated healthy controls. A total of 12 OCTN1 variants within exonic sequences were examined. Two nonsynonymous SNPs, rs1050152 (L503F) and rs272879 (L395V) were genotyped by a PCR-based RFLP/cRFLP method and statistically analyzed. These samples with an additional 141 unrelated healthy samples were also genotyped for rs1050152 using the SNPlex? Genotyping System.ResultsThe OCTN1 rs1050152 is associated with CD (OR = 1.745, 95% CI = 1.019–2.990, χ² = 4.129, p = 0.042) and with IBD (OR = 1.68, 95% CI = 1.052–2.676, χ² = 4.732, p = 0.030); while the variant rs272879 is not associated with IBD, CD or ulcerative colitis (UC). The distribution of the rs1050152 variant showed a high level of the T allele in male UC (OR = 2.585, 95% CI = 1.139–5.869, p = 0.023) and IBD (OR = 2.039, 95% CI = 1.024–4.059, p = 0.042) patients, and in female CD patients (OR = 2.329, 95% CI = 1.038–5.226, ρ value = 0.039).ConclusionThe present results replicated the association of the OCTN1 rs1050152 (L503F) variant with CD and IBD overall. A weak gender-specific effect of rs1050152 (L503F) on male UC and female CD was observed.     

Fibrinogen-to-albumin ratio is related to the severity of coronary artery disease in chronic kidney disease patients undergoing coronary angiography

ObjectivesThis study was to explore the potential relationship between the fibrinogen-to-albumin ratio (FAR) and the presence and severity of coronary artery disease (CAD) in stage 3–5 predialysis chronic kidney disease (CKD) patients.DesignThis study included 978 patients undergoing coronary angiography (CAG). CAD was defined as the presence of obstructive stenosis > 50% of the lumen diameter in any of the four main coronary arteries. Gensini scores (GSs), left main coronary artery (LMCA) and three-vessel coronary artery disease (TVD) were used to elevate the severity of CAD.ResultsThe adjusted odds ratios of CAD were 3.059 (95% CI: 1.859–5.032) and 2.670 (95% CI: 1.605–4.441) in the third and fourth quartiles of FAR compared with the first quartile, respectively. Among 759 patients diagnosed with CAD, multivariate logistic regression analysis showed that FAR (at the 0.01 level) was significantly positively associated with the presence of LMCA (adjusted OR = 1.177, 95% CI 1.067–1.299, P = 0.001) or TVD (adjusted OR = 1.154, 95% CI 1.076–1.238, P < 0.001), and a higher GS (adjusted OR = 1.152, 95% CI 1.073–1.238, P < 0.001).ConclusionsFAR levels were independently associated with the presence and severity of CAD in stage 3–5 predialysis CKD patients.