ABCB1 haplotype is associated with major molecular response in chronic myeloid leukemia patients treated with standard-dose of imatinib

BackgroundImatinib mesylate (IM) is a selective tyrosine kinase inhibitor used for treating chronic myeloid leukemia (CML). IM has high efficacy, however some individuals develop a resistance due to impaired bioavailability. Polymorphisms in genes encoding membrane transporters such as ABCB1 have been associated with differences in protein expression and function that influence the response to several drugs.AimTo investigate the relationship of ABCB1 polymorphisms with markers of response to IM in patients with CML.MethodsOne hundred eighteen CML patients initially treated with a standard dose of IM (400 mg/day) for 18 months were selected at two health centers in Sao Paulo City, Brazil. The response criteria were based on the European LeukemiaNet recommendations. ABCB1 polymorphisms c.1236C > T (rs1128503), c.3435C > T (rs1045642) and c.2677G > T/A (rs2032582) were evaluated by PCR-RFLP.ResultsABCB1 polymorphisms were not related with a risk for CML in this sample population (p < 0.05). In the CML group, frequencies of ABCB1 SNPs were similar between responder and non-responder patients (p > 0.05). In the responder group, the frequency of ABCB11236CT/2677GT/3435CT haplotype was higher in patients with major molecular response (MMR) (51.7%) than in patients without MMR (8.3%, p = 0.010). Furthermore, carriers of this haplotype had increased the probability of reaching the MMR compared with the non-carriers (OR: 11.8; 95% CI: 1.43–97.3, p = 0.022).ConclusionsThe ABCB1 1236CT/2677GT/3435CT haplotype is positively associated with the major molecular response to IM in CML patients.     

IL1B genetic variation and plasma C-reactive protein level among young adults: the CARDIA study

ObjectiveInterleukin-1B (IL1B) modulates C-reactive protein (CRP) expression. However, whether IL1B genetic variation is associated with CRP level is unknown. Further, obesity, a state of low-grade inflammation that influences cellular IL-1 functions may modify this association.Methods and resultsStudy participants (N = 3289), 48% blacks and 52% whites, had CRP level measurements at year 7 and year 15 examinations as part of the CARDIA study. Ten tag single nucleotide polymorphisms (SNPs) that characterize common IL1B gene variation were genotyped. In SNP analysis, no significant associations with either level or change in time CRP were observed after multiple testing adjustments. However, global ILIB gene variation was associated with year 7 to year 15 change in CRP (global nominal p = 0.004, multiple testing corrected p = 0.048) among obese blacks. Compared to the commonest haplotype, a common haplotype that includes the SNP rs1143642 was associated with greater increases in CRP from year 7 to year 15 among obese blacks and whites while another common haplotype that includes the SNP rs3917356 was associated with decreased change in CRP from year 7 to year 15 among obese blacks. The rare alleles of ILIB SNPs, SNP 7114 (rs1143642) and SNP 3298 (rs3917356), were associated with greater increases and decreases in CRP from year 7 to year 15 among blacks, respectively, compared to their common variants.ConclusionIL1B genetic variation may have a role in CRP level regulation and this association may be modified by obesity.     

IL6, IL10 and TGFB1 gene polymorphisms in coeliac disease: differences between DQ2 positive and negative patients

Predisposition to coeliac disease (CD) might be partially due to an individual pattern of hyper-inflammatory biased immune response. One of these patterns of intense response may be linked to the haplotype carrying HLA-DQ2 alleles and TNF −308A allele. However, 10 % of CD patients do not express the DQ2 heterodimer and these do not usually carry the TNF −308A allele. A similar response might be achieved by genes codifying other cytokines.ObjectivesTo study biallelic polymorphisms in genes codifying for TNFα, IL10, IL6 and TGFβ1 in DQ2 negative CD patients and to compare the results with DQ2 positive patients and healthy controls, in order to establish whether any of these polymorphisms have a role in CD susceptibility.MethodsTNF −308 (G > A), IL-6 −174 (G > C) and TGFB1 codon 10 (+ 869, T > C) and codon 25 (+ 915, G > C) polymorphisms and IL-10 haplotype of polymorphisms in positions −1082 (G > A), −819 (C > T) and −592 (C > A) were typed by a SSP-PCR technique.ResultsThe distribution of allele frequencies for TNF −308 is different between DQ2 positive CD patients and controls and the same occurs for haplotype frequencies of the IL10 promoter (−1082, −819, −592): The frequencies of the TNF −308A allele (p = 0.027), TNF −308A carriers (p = 0.031) and of IL10GCC haplotype are increased (p = 0.013) in DQ2 positive CD patients. However, the IL6 −174 allele G is more frequent in DQ2 negative patients than in healthy controls (p = 0.018), DQ2 negative controls (p = 0,018), and DQ2 positive patients (p = 0.008).ConclusionsDQ2 negative CD patients show an increased frequency of genotypes associated to IL6 high production. These were mainly allele G homozygous for the IL6 gene (−174) polymorphism. The IL6 −174GG genotype (homozygous) may be an additional risk marker for CD in DQ2 negative patients, representing an alternative susceptibility factor for CD when TNF −308A is negative.     

Polymorphisms of POR, SULT2A1 and HSD11B1 in children with premature adrenarche

Premature adrenarche (PA) refers to an earlier than normal increase in adrenocortical androgen production. The pathogenesis of PA remains largely unknown. We hypothesized that common polymorphisms at P450 oxidoreductase (POR), steroid sulfotransferase (SULT2A1), or 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1) genes could contribute to the polygenic pathogenesis of PA. We performed a case–control study on the polymorphisms rs1057868 at POR, rs182420 at SULT2A1, and rs12086634 at HSD11B1. The study cohort comprised 73 prepubertal children with PA (defined by clinical signs) and 97 age- and gender-matched healthy controls from a Finnish Caucasian population. Genotype distributions and clinical and metabolic phenotypes were determined. The genotype distributions of the polymorphisms were similar between the study groups. No variant was associated with alterations in serum adrenal steroid concentrations. The minor C variant at SULT2A1 was associated with higher serum sex hormone binding globulin (SHBG) concentrations (T/T, n = 64 vs T/C&;C/C, n = 33; mean 94 vs 116 nmol/L; P = .001) and a trend for lower dehydroepiandrosterone sulfate/dehydroepiandrosterone ratios in the controls (P = .06), and with higher plasma total cholesterol concentrations in the PA subjects (T/T, n = 42 vs T/C&;C/C, n = 31; 4.0 vs 4.6 mmol/L; P < .001). The minor G variant at HSD11B1 was associated with lower plasma triglyceride concentration in the controls (T/T, n = 65 vs T/G&;G/G, n = 32; 0.61 vs 0.49 mmol/L; P = .013). Common polymorphisms at POR, SULT2A1 or HSD11B1 were not associated with PA in a Finnish Caucasian population.     

Polymorphisms of LTA, LGALS2, and PSMA6 genes and coronary atherosclerosis: a pathological study of 1503 consecutive autopsy cases

ObjectiveRecent genome-wide association studies have identified polymorphisms of lymphotoxin-α (LTA), galectin-2 (LGALS2), and proteasome subunit a type 6 (PSMA6) genes as genetic risk factors for myocardial infarction (MI). However, their effects on coronary atherosclerosis, an intermediate phenotype of MI, remain largely unknown.MethodsWe investigated the correlation between polymorphisms of the LTA, LGALS2, and PSMA6 genes and the severity of pathological coronary stenosis index (CSI) and MI in 1503 consecutive autopsy cases of Japanese elderly patients.ResultsThe polymorphisms LTA rs1041981 and LGALS2 rs7291467 were associated with CSI with odds ratios of 1.54 (95% CI, 1.17–2.01; AA + CA over CC) and 1.62 (95% CI, 1.11–2.37; TT over CC + CT), respectively. PSMA6 rs1048990 was not associated with CSI. None of the SNPs was associated with MI in our sample.ConclusionOur findings indicate that the LTA and LGALS2 polymorphisms affect the subclinical phenotype of the coronary artery, which predisposes to the incidence of MI.     

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.     

FADS gene polymorphisms in Koreans: association with ω6 polyunsaturated fatty acids in serum phospholipids, lipid peroxides, and coronary artery disease

ObjectiveWe investigated the association of polymorphisms in FADS genes with polyunsaturated fatty acids (PUFAs) in serum phospholipids, lipid peroxides, and coronary artery disease (CAD) in Koreans.MethodsIn this case–control study, CAD patients (n = 756, 40–79 years) and healthy controls (n = 890) were genotyped for rs174537 near FADS1 (FEN1 rs174537G > T), FADS2 (rs174575, rs2727270), and FADS3 (rs1000778). We calculated the odds ratios (ORs) for CAD risk and measured serum PUFA composition and lipid peroxide.ResultsAmong four SNPs, only rs174537G > T differed in allele frequencies between controls and CAD patients after adjustment for age, BMI, cigarette smoking, alcohol consumption, hypertension, diabetes mellitus, and hyperlipidemia (P = 0.017). The minor T allele was associated with a lower risk of CAD [OR 0.75 (95%CI 0.61–0.92), P = 0.006] after adjustment. rs174537T carriers had a significantly higher proportion of linoleic acid (LA, 18:2ω6), lower arachidonic acid (AA, 20:4ω6), and lower ratios of AA/dihomo-γ-linolenic acid (DGLA, 20:3ω6) and AA/LA than G/G subjects in both control and CAD groups. In the control group, 174537T carriers had significantly lower levels of total- and LDL-cholesterol, malondialdehyde, and ox-LDL. In CAD patients, rs174537T carriers showed a larger LDL particle size than G/G subjects. The proportion of AA in serum phospholipids positively correlated with LDL-cholesterol, ox-LDL, and malondialdehyde in controls and with 8-epi-prostaglandin F_2α in both control and CAD groups.ConclusionThe rs174537T is associated with a lower proportion of AA in serum phospholipids and reduced CAD risk, in association with reduced total- and LDL-cholesterol and lipid peroxides.     

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.     

Akt2 Gene common allelic variants in insulin resistance and the metabolic syndrome

Background and aimSeveral lines of evidence indicate that glucose homeostasis may be under the control of Akt2 and it can therefore be seen as a candidate gene for human insulin resistance (IR) and related phenotypes. The aim of our study was the identification of Akt2 common allelic variants that might modulate susceptibility to IR and related metabolic abnormalities.Methods and resultsThe Akt2 gene (exons, 5′ and 3′ regulatory regions) was re-sequenced in samples of 50 blood donors from the Gargano region. Two single nucleotide polymorphisms (SNPs) in 5′ (rs11669332 and rs969531) and two in 3′ (rs2304186 and C1658T) regulatory regions were exploited in an association study using 661 healthy unrelated Caucasian individuals from the same region.Individuals being homozygous for the T allele of rs11669332 (an Akt2 promoter) showed lower systolic blood pressure (p = 0.04), total/HDL cholesterol ratio (p = 0.02) and the metabolic syndrome score (p = 0.04), while carriers of the A allele of rs969531 (in 5′-UTR) showed higher systolic blood pressure (p = 0.027). The association between phenotypic traits and possible haplotypes was tested as well. However, no haplotype affecting the risk of metabolic abnormalities was found.ConclusionsTwo variants in 5′ regulatory region of Akt2 gene are associated and may modulate susceptibility to IR and related metabolic abnormalities.     

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.     

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.     

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.     

Investigation of SLC2A1 26177A/G gene polymorphism via high resolution melting curve analysis in Malaysian patients with diabetic retinopathy

PurposeIn this study, we aimed to investigate the possible association between SLC2A1 26177A/G polymorphism and diabetic retinopathy (DR) in Malaysian patients with type 2 diabetes.MethodsGenomic DNA was extracted from 211 Malaysian type 2 diabetic patients (100 without retinopathy [DNR], 111 with retinopathy) and 165 healthy controls. A high resolution melting assay developed in this study was used to detect SLC2A1 26177A/G polymorphism followed by statistical analysis.ResultsA statistically significant difference in 26177 G minor allele frequency between healthy controls (19.7 %) and total patient group (26.1 %) (p < 0.05, Odd ratio = 1.437, 95% Confidence interval = 1.015–2.035) as well as between healthy controls (19.7 %) and DNR patients (27.5%) (p < 0.05, Odd ratio = 1.546, 95% Confidence interval = 1.024–2.336) was shown in this study. However, when compared between DR and DNR patients, there was no significant difference (p > 0.05).ConclusionsThis is the first study which shows that SLC2A1 26177G allele is associated with type 2 diabetes in Malaysian population but not with DR.     

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.     

Prevalence and determinants of undiagnosed diabetes in an urban sub-Saharan African population

AimsTo report the prevalence of undiagnosed diabetes and its determinants among adults Cameroonian urban dwellers.MethodsOn May 17th 2011, a community-based combined screening for diabetes and hypertension was conducted simultaneously in four major Cameroonian cities. Adult participants were invited through mass media. Fasting blood glucose was measured in capillary blood.ResultsOf the 2120 respondents, 1591 (52% being men) received a fasting glucose test. The median age was 43.7 years, and 64.2% were overweight or obese. The sex-specific age adjusted prevalence (for men and women) were 10.1% (95% confidence interval [CI]: 8.1–12.1%) and 11.2% (95%CI: 9.1–13.3%) for any diabetes, and 4.6% (95%CI: 2.6–6.6%) and 5.1% (95%CI: 3.0–7.2%) for screened-detected diabetes, respectively. The prevalence of diabetes increased with increasing age in men and women (all p ≤ 0.001 for linear trend). Older age (p < 0.001), region of residence (p < 0.001), excessive alcohol intake (p = 0.02) were significantly associated with screened-detected diabetes, while physical inactivity, body mass index, and high waist girth were not significantly associated with the same outcome.ConclusionsPrevalence of undiagnosed diabetes is very high among Cameroonian urban dwellers, indicating a potentially huge impact of screening for diabetes, thus the need for more proactive policies of early detection of the disease.     

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.     

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.     

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.