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.     

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.     

Allelic variations of the vitamin D receptor (VDR) gene are associated with increased risk of coronary artery disease in type 2 diabetics: The DIABHYCAR prospective study

AimVitamin D deficiency is associated with coronary artery disease (CAD), and the actions of vitamin D are mediated by binding to a specific nuclear vitamin D receptor (VDR). This study investigated the associations of VDR gene variants with CAD in two cohorts of type 2 diabetes patients.MethodsA cohort of 3137 subjects from the prospective DIABHYCAR study (CAD incidence: 14.8%; follow-up: 4.4 ± 1.3 years) and an independent, hospital-based population of 713 subjects, 32.3% of whom had CAD, were assessed. Three SNPs in the VDR gene were genotyped: rs1544410 (BsmI); rs7975232 (ApaI); and rs731236 (TaqI).ResultsIn the DIABHYCAR cohort, an association was observed between the A allele of BsmI and incident cases of CAD (HR: 1.16, 95% CI: 1.05–1.29; P = 0.002). Associations were also observed between BsmI (P = 0.01) and TaqI (P = 0.04) alleles and baseline cases of CAD. The AAC haplotype (BsmI/ApaI/TaqI) was significantly associated with an increased CAD prevalence at the end of the study compared with the GCT haplotype (OR: 1.12, 95% CI: 1.02–1.28; P = 0.04). In a cross-sectional study of the independent hospital-based cohort, associations of ApaI (P = 0.009) and TaqI (P = 0.03) alleles with CAD were observed, with similar haplotype results (OR: 1.33, 95% CI: 1.03–1.73; P = 0.03).ConclusionThe haplotype comprising the minor allele of BsmI, major allele of ApaI and minor allele of TaqI of VDR (AAC) was associated with an increased risk of CAD in type 2 diabetes patients. This effect was independent of the effects of other known cardiovascular risk factors.     

基质金属蛋白酶2基因多态性与缺血性收缩性心衰预后相关

目的基质金属蛋白酶家族（Matrix metalloproteinases,MMPs）是一组蛋白溶解酶系,在心肌细胞外基质降解过程中发挥重要作用。MMP-2作为家族中的重要成员,在心力衰竭心肌重构过程中起关键作用。我们推测MMP-2基因多态性可能会影响收缩性心衰的预后。方法对387位缺血性收缩性心衰患者进行随访,用限制性片段长度多态性的方法（restriction fragment length polymorphism,RFLP）分析MMP-2基因的三个单核苷酸多态性（single nucleotide polymorphisms,SNPs）位点rs243864,rs243866,rs17859821。结果随访到335位患者,随访率86．6％。在随访期间（0～47个月,中位随访时间24个月）,有72例（21．5％）患者死亡,56例（16．7％）患者因心衰再次入院,3例（0．9％）患者再次心肌梗塞,24例（7．2％）再次血运重建。1年、2年、3年的生存率分别是86％、79％、73％。MMP-2 rs17859821 A等位基因携带者全因死亡率、心源性死亡率、心衰死亡率和主要心脏不良事件率（major adveme cardiac event,MACE）均高于GG基因型者（OR=0．513,0．416,0．472,0．671;P=0．010,0．002,0．021,0．022）。使用Cox回归分析校正年龄、束支传导阻滞、LVEF和NYHA分级后,A等位基因携带者心源性死亡率和心衰死亡率仍显著或临界显著低于GG基因型者（OR=0．475,0．518;P=0．010,0．050）。结论研究结果提示携带MMP-2 rs17859821A等位基因的缺血陛收缩性心衰患者预后较好。     

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.     

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.     

Chimerin 2 genetic polymorphisms are associated with non-proliferative diabetic retinopathy in Taiwanese type 2 diabetic patients

AimTo investigate whether chimerin 2 (CHN2) genetic polymorphisms were associated with the susceptibility to diabetic retinopathy (DR) in Taiwanese individuals with type 2 diabetes.MethodsThis case-control study comprised of 171 individuals with DR and 548 without DR. Four rs39059, rs2023908, rs1002630 and rs1362363 polymorphism of CHN2 were genotyped for each subjects. All subjects underwent a complete ophthalmologic examination, and basic information (age, gender, age at diagnosis of diabetes, and ocular history of the patient) was record. Several clinical parameters (systolic and diastolic blood pressure, waist and hip circumferences, body mass index levels, fasting glucose and HbA1c) were measured.ResultsLogistic regressions were used to analyze odds ratios between SNPs and DR after controlling for gender, systolic blood pressure, waist and hip ratio, duration of diabetes, serum HbA1c levels and nephropathy classification. A protective effect of rs1002630 (GA + AA) and rs1362363 (AG + GG) [odds ratio (OR) (95% confidence interval) = 0.45 (0.22–0.88), 0.66 (0.44–0.99), respectively) was observed. Furthermore, the protective effect of rs1002630 was observed when compared subjects with non-proliferative DR with subjects without DR [OR = 0.25 (95%C.I. = 0.09–0.73)].ConclusionsThis study showed that the rs1002630 of CHN2 were associated with DR risk and non-proliferative DR risk in Taiwanese individuals with type 2 diabetes. Variations at this locus may contribute to the pathogenesis of DR.     

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.     

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.     

Association of MMP-2 genes variants with diabetic retinopathy in Tunisian population with type 2 diabetes

AimsFew studies investigated the association of genetic difference in metalloproteinase-2 (MMP-2) gene with diabetic retinopathy but with mixed outcome. To investigate the association between a set of MMP-2 genetic variants and the risk of diabetic retinopathy in an Arab Tunisian population with type 2 diabetes.Subjects and methodsA retrospective case-control study comprising a total of 779 type 2 diabetes patients with or without diabetic retinopathy was conducted. Genotyping was prepared by TaqMan® SNP genotyping qRT-PCR. The variants used were rs243865 (C/T), rs243864 (T/G), rs243866 (G/T) and rs2285053 (C/T).ResultsThe minor allele frequency (MAF) of the rs243864 MMP-2 variant was significantly higher among diabetic retinopathy patients. Setting homozygous wild type genotype carrier as reference, the rs243864T/G allele was associated with increased risk of diabetic retinopathy under the dominant, recessive, and additive models which persisted when key covariates were controlled for, while a reduced risk of diabetic retinopathy progression was seen after adjustment between non-proliferative and proliferative diabetic patients. Furthermore, the heterozygous genotype GT of the rs243866 variant is positively associated with the risk of proliferative diabetic retinopathy in the additive model. A limited linkage disequilibrium (LD) was revealed between the four-matrix metalloproteinase-2 variants. Four-loci haplotype analysis identified, GCTC, TTTC, and GCTT haplotypes to be positively associated with the risk of diabetic retinopathy.ConclusionOur findings demonstrate that the MMP-2 variant rs243864 and 243866 are related to the susceptibility to diabetic retinopathy and the progression of the disease in an Arab Tunisian population with type 2 diabetes.     

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.     

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.     

Polymorphisms of Adrenoceptors are Not Associated With an Increased Risk of Adverse Event in Heart Failure: A MERIT-HF Substudy

BackgroundEnhanced sympathetic activation has a central role in the development of heart failure (HF). We assessed whether the α_2C-adrenoceptor (Del322-325) polymorphism exclusively or in combination with a β₁-adrenoceptor (Arg389) polymorphism, each with known independent effects on sympathetic function, were associated with an increased risk of adverse events in HF.Methods and ResultsA total of 526 patients enrolled in the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure study were genotyped for both adrenoceptor polymorphisms. The distribution of α_2C genotypes was similar between the event and nonevent groups. However, a reduced prevalence of the Del322-325 allele was found in individuals with ischemic congestive HF (P = .022). Patients possessing both the α_2C Del322-325 and β₁ Arg389 alleles had no increased risk of events. Adjusting for confounding variables and the β₁ Arg389Gly polymorphism, the odds ratio of being ins/del + del/del for the α_2C Del322-325 and having an event was 0.89 with 95% CI 0.49–1.63, P = .715. Similarly, adjusting for confounding variables and the α_2C Del322-325 polymorphism the odds ratio of being Arg/Arg or Arg/Gly for the β₁ Arg389Gly polymorphism and having an event was 1.13 with 95% CI 0.52–2.17, P = .864.ConclusionsThe α_2C Del322-325 polymorphism exclusively or in combination with the β₁Arg389 allele is not associated with an increased risk of adverse events in HF.     

No impact of interleukin-28B polymorphisms on spontaneous or drug-induced hepatitis delta virus clearance

Backgroundrs12979860 and rs8099917 interleukin-28B polymorphisms are associated with spontaneous or interferon-alpha induced hepatitis C clearance, “CC” and “TT” genotypes (respectively) being the most favourable. There are no data on the influence of interleukin-28B polymorphisms on hepatitis delta clearance in hepatitis B/D co-infected patients.AimsThe present study explores the potential influence of both rs12979860 and rs8099917 polymorphisms on delta infection outcome.MethodsRetrospective-longitudinal study on 55 European patients observed for at least 4 years, selected from a cohort of 439 subjects positive for hepatitis delta antibodies and hepatitis B core antibodies.The rate of spontaneous and interferon induced delta-RNA clearance was compared in interleukin-28B rs12979860 “CC” vs “non CC”, and in rs8099917 “TT” vs “non TT” genotypes.ResultsPrevalence of rs12979860 C allele was 60%, consistent with the reported prevalence in Italy (67%, p = 0.128). No significant differences in spontaneous clearance rate were observed between rs12979860 “CC” and “non CC” genotypes (13.3% vs 7.5%, respectively, p = 0.60), and between rs8099917 “TT” and “non-TT” genotypes (11.1 vs 7.1%, respectively, p = 0.67). No differences were observed for interferon-induced delta-RNA clearance either.ConclusionsOur data suggest that interleukin-28B polymorphisms might not influence hepatitis delta clearance rate in either natural history or interferon-alpha response.     

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.     

Interacción cardiorrenal y evolución de la insuficiencia cardiaca. ¿Tiene un papel la proteína de unión del factor de crecimiento de tipo insulina 2?

Introduction and objectivesPreliminary results suggest that high circulating insulin-like growth factor binding protein 2 (IGFBP2) levels are associated with mortality risk in heart failure (HF) patients. As IGFBP2 levels are increased in patients with chronic kidney disease (CKD), which is associated with a higher mortality risk in HF patients, we examined whether IGFBP2 is associated with CKD in HF patients, and whether CKD modifies the prognostic value of this protein in HF patients.MethodsHF patients (n = 686, mean age 66.6 years, 32.7% women) were enrolled and followed up for a median of 3.5 (min-max range: 0.1-6) years. Patients were classified as having CKD with decreased estimated glomerular filtration rate (eGFR < 60 mL/min/1.73 m²) or as having CKD with nondecreased eGFR (≥ 60 mL/min/1.73 m²). Serum IGFBP2 was detected by ELISA.ResultsIGFBP2 was increased (P < .001) in CKD patients with decreased eGFR (n = 290, 42.3%) compared with patients with nondecreased eGFR. IGFBP2 was directly associated with NT-proBNP (P < .001) and inversely associated with eGFR (P < .001), with both associations being independent of confounding factors. IGFBP2 was directly and independently associated with cardiovascular and all-cause death (P < .001) in the whole group of patients, but showed a stronger association with cardiovascular death in CKD patients with decreased eGFR (P for interaction < .05), improving risk prediction in these patients over clinically relevant risk factors.ConclusionsSerum IGFBP2 is associated with impaired renal function and prognosticates cardiovascular death in patients with HF and CKD with decreased eGFR. Thus, there is an effect modification of CKD on circulating IGFBP2 and on its association with cardiovascular mortality in HF patients.     

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.     

Four complement factor H gene polymorphisms in association with AMD: A meta-analysis

AimTo investigate the possible association between CFH gene polymorphisms −543G > A (rs1410996), A473A (rs2274700), −257C > T (rs3753394), IVS15 (rs1329428) and AMD risk.MethodsWe searched the published literature in the Medline and Scopus from inception to May 2015. A meta-analysis was performed by the programs RevMan 5.1 and Stata 12.0, and the Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated in fixed or random effect model based on heterogeneity test among studies.ResultsNineteen studies with a total of 10,676 subjects were included in the present meta-analysis. A statistical significant association was observed between AMD risk and CFH −543G > A polymorphism with OR of 1.77 (95% CI, 1.47–2.12), 2.24 (95% CI, 1.71–2.94), 0.49 (95% CI, 0.38–0.62) and 0.25 (95% CI, 0.18–0.37) in additive, dominant, recessive and codominant models, respectively. Similar results were obtained in polymorphisms A473A, −257C > T, IVS15. Furthermore, stratified analysis for ethnicity showed a significantly strong association between −543G > A, A473A polymorphisms and AMD risk.ConclusionThe present meta-analysis suggested that CFH −543G > A, A473A, −257C > T, and IVS15 polymorphisms might be moderately associated with AMD risk. This conclusion warrants confirmation by further studies.     

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.     

KCNK17 genetic variants in ischemic stroke

BackgroundGenetic factors contribute to the development of ischemic stroke (IS). In order to identify susceptibility variants, we analyzed single nucleotide polymorphisms (SNPs) that had been previously linked to stroke in a genome-wide association study.MethodsWe analyzed 12 SNPs in a White population comprising IS patients and healthy controls. The analysis was adjusted for confounding variables and stratified by stroke etiology. Functional studies were then performed to elucidate the role of these variants in IS.ResultsIn a preliminary analysis of 268 controls and 531 IS cases, the rs10947803 SNP of KCNK17 (p = 0.012) and the rs7506045 of IMPA2 (p = 0.040) were associated with IS, although only the KCNK17 gene was an independent risk factor for IS. In a second phase, analysis of 271 new IS cases revealed that the A allele of rs10947803 was associated with stroke after correction for Bonferroni (OR = 1.48; 95% CI, 1.14–1.91, p = 0.003). Gene expression analysis revealed that KCNK17 mRNA levels were higher in the IS cases in the acute phase than in controls (14 ± 78% vs. 91 ± 41, p = 0.002) but not in the chronic phase (56 ± 57%; p = 0.230). Moreover, RNA levels depended on the alleles of the rs10947803 SNP in the control group (p = 0.021) and in the chronic phase (p = 0.033).ConclusionsThe A allele of the rs10947803 variant of KCNK17 was associated with increased risk of IS and increased levels of KCNK17 gene expression. The role of this potassium channel gene in IS opens diagnostic and therapeutic expectations and merits further investigation.