Association of the −33C/G <Emphasis Type="Italic">OSF</Emphasis>-<Emphasis Type="Italic">2</Emphasis> and the 140A/G <Emphasis Type="Italic">LF</Emphasis> gene polymorphisms with the risk of chronic rhinosinusitis with nasal polyps in a Polish population

Nasal polyps are strongly associated with a risk of chronic rhinosinusitis development as well as other obstruction including asthma and allergy. The following study tested the association of the 140A/G polymorphism of lactoferine (LF) encoding gene and the −33C/G polymorphism of osteoblast-specific factor-2 (OSF-2) encoding gene with a risk of chronic rhinosinusitis with nasal polyps in a Polish population. One hundred ninety five patients of chronic rhinosinusitis with nasal polyps as well as 200 sex, age and ethnicity matched control subjects without chronic sinusitis and nasal polyps were enrolled in this study. Among the group of patients 63 subjects were diagnosed with allergy and 65 subjects with asthma, respectively. DNA was isolated from peripheral blood lymphocytes of patients as well as controls and gene polymorphisms were analyzed by restriction fragments length polymorphism polymerase chain reaction (RFLP-PCR). We reported that the 140A/G LF (OR 4.78; 95% CI 3.07–7.24), the −33C/G OSF-2 OR 3.48; 95% CI 2.19–5.52) and the −33G/G OSF-2 (OR 16.45; 95% CI 6.71–40.30) genotypes were associated with an increased risk of chronic rhinosinusitis with nasal polyps among analyzed group of patients. Moreover, the group of patients without allergy or asthma indicated the association of the −33C/G (OR 3.72; 95% CI 2.24–6.19 and OR 15.11; 95% CI 5.91–38.6) and −33G/G (OR 3.73; 95% CI 2.24–6.19 and OR 14.07; 95% CI 5.47–36.16) genotypes of the OSF-2 as wells as 140A/G (OR 3.89; 95% CI 2.40–6.31 and OR 3.62; 95% CI 2.45–5.34) genotype of OSF-2 with an increased risk of chronic rhinosinusitis with nasal polyps. Finally, it was also found that the selected group of patients with allergy or asthma indicated a very strong association of the −33C/G (OR 2.40; 95% CI 1.23–4.69 and OR 2.40; 95% CI 1.23–4.69, respectively) and −33G/G (OR 16.01; 95% CI 5.77–44.41 and OR 17.90; 95% CI 6.53–49.05, respectively) genotypes of the OSF-2 as wells as 140A/G (OR 3.22; 95% CI 1.74–6.11 and OR 3.25; 95% CI 1.75–6.04, respectively) genotypes with an increased risk of chronic rhinosinusitis with nasal polyps. Thus, our results suggest that LF and OSF-2 gene polymorphisms may have deep impact on the risk of rhinosinusitis nasal polyps’ formation which may also depend on asthma or allergy. Our results showed that the 140A/G polymorphism of LF gene and the −33C/G polymorphism of the OSF-2 gene may be associated with the risk of chronic rhinosinusitis with nasal polyps in a Polish population.     

A meta-analysis on the association between three promoter variants of TNF-α and Crohn’s disease

Tumor necrosis factor-alpha (TNF-α) has been regarded as a candidate gene for Crohn’s disease (CD) based on its inflammatory function in immune reaction and the clinical effectiveness of anti-TNF-α therapy. However, studies to date have reported inconsistent findings for the association between TNF-α and CD. The PubMed, EMBASE, and Medline databases were systematically reviewed from all English language publications up to April, 2011. A total of twenty-nine studies concerning the association between CD and the TNF-α promoter polymorphisms of −308G/A, −857C/T and −238G/A were identified, among of them only twenty-three studies match the inclusion criteria (including 3,843 cases and 6,260 controls) and were selected for the statistical test. We found that neither the G allele of −308G/A (OR 1.02, 95% CI 0.87–1.19, P = 0.84), C allele of −857C/T (OR 0.97, 95% CI 0.86–1.09, P = 0.57) and G allele of −238G/A (OR 0.91, 95% CI 0.70–1.18, P = 0.48), and nor their GG (OR 1.05, 95% CI 0.88–1.25, P = 0.59), CC (OR 0.98, 95% CI 0.86–1.12, P = 0.76) and GG (OR 0.92, 95% CI 0.70–1.21, P = 0.55) genotypes were associated with CD susceptibility, respectively. Our meta-analysis demonstrates that three promoter polymorphisms of TNF-α above may not confer susceptibility to CD.     

Association of chromosome 8q24 variants with prostate cancer risk in the Siberian region of Russia and meta-analysis

Compelling evidence demonstrates the importance of chromosome 8q24 as a locus of susceptibility to prostate cancer. In this work, the association of common 8q24 variants, rs6983267 and rs1447295, with a sporadic risk of prostate cancer was analyzed in the Russian population of Siberia. For this purpose, the above polymorphisms were genotyped in 393 cases and 384 control individuals. The A allele of rs1447295 was significantly associated with prostate cancer risk (OR[CI 95%] = 1.74 [1.26–2.4], p = 7.8 × 10⁻⁴). The common G-A haplotype of rs6983267-rs1447295 also showed association with prostate cancer risk in Russians (OR[CI 95%] = 2.03 [1.1–3.75], p = 0.02). A meta-analysis combining our data with previously published results was performed to better evaluate the association between the SNPs studied and prostate cancer risk; its results strongly supported the association for both loci (p < 10⁻⁶). Thus, our study has confirmed the association of chromosome 8q24 with a risk of prostate cancer.     

ABO blood group polymorphisms and risk for ischemic stroke and peripheral arterial disease

Recent studies have demonstrated association between ABO blood system and thrombosis, indicating that individuals belonging to non-O blood groups (A, B or AB) present an increased risk of venous thrombosis, heart disease, and ischemic stroke (IS) as compared to O blood group carriers. In this study, we investigated the frequency of ABO blood group polymorphisms and its association with IS and peripheral arterial disease. Significant differences were observed for O1 (OR 0.57, 95 % CI 0.35–0.95, p < 0.05) and O2 (OR 3.47, 95 % CI 1.15–10.28, p < 0.05) alleles among IS patients while significant differences were observed for B phenotype (26.3 vs 9.5 %, OR 3.42, 95 % CI 1.32–8.76, p = 0.01, patients vs controls, respectively) and alleles A1 (OR 0.31, 95 % CI 0.11–0.84, p < 0.05), O2 (OR 4.61, 95 % CI 1.59–13.23, p < 0.01) and B (OR 3.42, 95 % CI 1.62–7.13, p < 0.001) alleles for PAD patients. O1 allele was an independent variable (OR 0.27, 95 % CI 0.12–0.57, p < 0.001) for IS patients. These data suggest the relationship of non-O blood groups in pathogenesis of thrombosis events and a possible protective effect of O blood group.     

The APOE4 allele is associated with a decreased risk of retinopathy in type 2 diabetics

Background

Common polymorphisms within the apolipoprotein E (APOE) gene are suggested to be associated with the development of type 2 diabetes mellitus (T2DM), but the potential association with T2DM complications (nephropathy, neuropathy and retinopathy) remains unclear. We perform the case–control study to analyse the association between the APOE polymorphism and risk of T2DM and to analysed the potential relationship between the APOE and T2DM complications.

Methods and results

APOE variants (rs429358 and rs7412) were genotyped by TaqMan assay in T2DM patients (N?=?1274; N?=?829 with complications including retinopathy, neuropathy and nephropathy status) and with PCR–RFLP in healthy nondiabetic controls (N?=?2055). The comparison of subjects with genotypes associated with low plasma cholesterol (APOE2/E2 and APOE2/E3 carriers vs. others) did not show an association with T2DM (OR [95% CI]?=?0.88 [0.71–1.08). The differences remained insignificant after adjusting for diabetes duration, sex and BMI. Carriers of at least one APOE4 allele (rs429358) are protected against T2DM related retinopathy (OR [95% CI]?=?0.65 [0.42–0.99]. Protection against retinopathy is driven mostly by females (OR [95% CI]?=?0.50 [0.25–0.99]); and remains significant (P?=?0.044) after adjustment for diabetes duration and BMI.

Conclusion

Common APOE polymorphism was not associated with T2DM in the Czech population. Yet, APOE4 allele revealed an association with retinopathy. In particular, female T2DM patients with at least one APOE4 allele exhibit lower prevalence of retinopathy in our study subjects.

     

A meta-analysis of HLA-DR polymorphism and genetic susceptibility to idiopathic dilated cardiomyopathy

Idiopathic dilated cardiomyopathy (IDC) has been hypothesized as a multifactorial disorder initiated by an environment trigger in individuals with predisposing human leukocyte antigen (HLA) alleles. Published data on the association between HLA-DR polymorphism and IDC risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 19 case–control studies including 1,378 cases and 10,383 controls provided data on the association between HLA-DR polymorphism and genetic susceptibility to IDC. Overall, statistically elevated frequencies of HLA-DR4 (OR 1.58; 95% CI 1.21–2.07; P = 0.0009) and HLA-DR5 (OR 1.35; 95% CI 1.05–1.73; P = 0.02) alleles were found in patients with IDC compared with controls. Individuals with HLA-DR3 antigen have a protective effect against IDC (OR 0.72; 95% CI 0.58–0.90; P = 0.004). In summary, this meta-analysis indicated that certain HLA-DR alleles may be genetic markers for susceptibility and resistance to IDC.     

Apolipoprotein E Polymorphism and Colorectal Neoplasm: Results from a Meta-Analysis

To investigate the relationship of Apolipoprotein E (APOE) gene polymorphism to colorectal neoplasia (CRN), we performed a systematic review and meta-analysis. Eligible studies were identified through a systematic literature review from PubMed, EMBASE, and the Science Citation Index up to February 2014. A combined analysis was performed, followed by a subgroup analyses stratified by the study design. We used data collected from 8 prospective studies involving respectively a total of 9243 participants and 4310 CRN cases which including 438 patients with colorectal adenoma (CRA), and 3873 patients with colorectal carcinoma (CRC). The pooled data from this meta-analysis indicated there was no significant association between APOE polymorphism and CRN (ε2: P = 0.51, OR 1.04 95% CI 0.93 to 1.16; ε4: P = 0.72, OR 0.98 95% CI 0.90 to 1.07). Interestingly, subgroup analysis demonstrated there was a significant decreased risk for proximal CRN in patients with APOE ε4 (P = 0.0007, OR 0.52 95% CI 0.35 to 0.76). Data showed no significant association between APOE genotype and overall CRN. However, compared with those carry APOE ε3 alleles, persons with APOE ε4 genotype have significant decreased risk suffering from proximal CRN but not from distal CRN.     

Association between α1-antichymotrypsin signal peptide −15A/T polymorphism and the risk of Alzheimer’s disease: a meta-analysis

No consensus has been recently reached at the relationship between the α1-antichymotrypsin (ACT) signal peptide −15A/T polymorphism and Alzheimer’s disease (AD) risk. Thus, our study aimed to better assess this association by performing a meta-analysis, including 4,212 cases and 4,039 controls from 29 studies. Odds ratios (ORs) with the 95% confidence interval (CI) were used to assess the strength of relationship between ACT −15A/T polymorphism and AD risk. Overall, a borderline statistically significant association was detected under recessive model comparison in all subjects (AA vs. AT+TT: OR 1.12, 95% CI 1.01–1.25, P = 0.04). But in subgroup analysis by ethnicity, no significant association was found in Caucasians, Asians, or Africans. Moreover, after exclusion of one study which affect the heterogeneity, the ACT A allele and AA genotype were statistically associated with late-onset AD (LOAD) risk (AA vs. TT: OR 1.25, 95% CI 1.06–1.48, P = 0.007, A vs. T: OR 1.12, 95% CI 1.03–1.21, P = 0.008), especially in Caucasians. In conclusion, our study suggests that the common α1-antichymotrypsin signal peptide −15A/T polymorphism may not be a major risk factor for AD. However, the polymorphism is capable of increasing LOAD risk.     

CCL2 −2518 A/G single nucleotide polymorphism as a risk factor for breast cancer

The contribution of the CCL2 −2518 A>G (rs 1024611) polymorphism in the occurrence and progression of various cancers has been found to be discordant. We studied the prevalence of the CCL2 −2518 A>G polymorphism in patients with breast cancer (n = 160) and controls (n = 323) in a sample of the Polish population. There were no significant differences in CCL2 −2518 A>G genotypes between patients with breast tumors and controls. Odds ratio (OR) for patients bearing the GG genotype was 1.481 (95% CI = 0.7711–2.845, P = 0.2358), and OR of the GG and AG genotypes was 0.7269 (95% CI = 0.4967–1.064, P = 0.1002). There was also no significant distinction in the prevalence of alleles between patients and healthy individuals. OR for the CCL2 −2518 G allele frequency was 0.8903 (95% CI = 0.6611–1.199, P = 0.4441). Analysis of the association between tumor size, lymph node metastases, histological grade, and distribution of genotypes and alleles for the CCL2 −2518 A>G polymorphism also did not show significant differences. Our results did not show association of the CCL2 −2518 A>G polymorphism with breast cancer occurrence and clinical characteristics in a sample of the Polish cohort.     

Influence of the inducible nitric oxide synthase gene (<Emphasis Type="Italic">NOS2A</Emphasis>) on inflammatory bowel disease susceptibility

The great amount of nitric oxide (NO) produced by the inducible isoform of NO synthase (iNOS) exerts deleterious effects, and iNOS expression is raised in the colonic mucosa of inflammatory bowel disease (IBD) patients. This is the first association analysis of polymorphisms within the NOS2A extended gene with IBD susceptibility. We analyzed 336 patients of Crohn’s disease (CD), 355 of ulcerative colitis (UC), and 536 healthy controls from a Spanish population. We tested a (CCTTT)n microsatellite, a (−/TAAA) insertion, and two single nucleotide polymorphisms (SNPs) flanking them (rs2779251 and rs2779248) in the NOS2A promoter, together with two SNPs in the coding region: one within exon 10, D385D (rs1137933), and another mapping to exon 16, S608L (rs2297518). Analysis of these markers evidenced differences among IBD patients and healthy controls. Allele (CCTTT) 13 is related to higher UC risk (p = 0.001; odds ratio [OR] [95% confidence interval, CI] = 1.64 [1.20–2.23]). Carriers of minor alleles of the two promoter SNPs analyzed showed an association with UC predisposition, and common allele homozygotes of the two exonic SNPs were more frequent among CD patients than among controls. Concordantly, one out of the three haplotypes carrying both exonic risk alleles was found to increase CD susceptibility (p = 0.007; OR [95%CI] = 1.74 [1.13–2.67]). Therefore, the NOS2A gene seems to be involved in IBD aetiology.     

Association of the genetic polymorphisms in immunoinflammatory microRNAs with risk of ischemic stroke and subtypes in an Iranian population

Stroke is one of the most common type of cerebrovascular disease threatening human health and life with high mortality, disability, and morbidity. Ischemic stroke (IS) is determined to be a complex disease containing a group of heterogeneous disorders with various environmental and genetic risk factors. This study evaluated the polymorphisms of microRNAs involved in inflammatory routes leading to stroke in an Iranian population. This study evaluated the associations of hsa-mir-608 C/G rs4919510, hsa-mir-499 A/G rs3746444, and hsa-mir-145 C/T rs190323149 polymorphisms in precursor miRNAs with the risk of IS. These microRNA polymorphisms were analyzed in 470 patients with IS and 489 control subjects. The TOAST criteria was applied for IS subtypes classification. The frequency of the allele G of hsa-mir-499/rs3746444 A/G revealed significant association with IS in comparison with controls ( p < 0.0001, OR = 1.838, 95% CI = 1.406–2.401). Increased IS risks were associated with hsa-mir-499/ rs3746444 A/G genotypes in diverse genetic model (homozygote comparison: p = 0.004, OR = 2.136, 95% CI = 1.269–3.597; heterozygote comparison: p = 0.029, OR = 1.373, 95% CI = 1.033–1.825). Statistical analysis in IS subtypes showed that cardio-embolic patients compared with other subtypes (large artery atherosclerosis and lacunar) had higher frequency of G allele (LAA vs. CEI, p = 0.017; LAC vs. CEI, p = 0.009), AG genotype (LAA vs. CEI, p = 0.016; LAC vs. CEI, p = 0.013). Nevertheless, this study did not find any association between the alleles and genotypes of mir-608 C/G rs4919510 SNP and IS, respectively ( p > 0.05). The current investigation provided verification that hsa-mir-499 rs3746444 A/G polymorphism may be associated with a significantly increased risk of IS in an Iranian population.     

Maternal cigarette smoking, metabolic gene polymorphisms, and preterm delivery: new insights on G×E interactions and pathogenic pathways

Preterm delivery (PTD, <37 weeks of gestation) is a significant clinical and public health problem. Previously, we reported that maternal smoking and metabolic gene polymorphisms of CYP1A1 MspI and GSTT1 synergistically increase the risk of low birth weight. This study investigates the relationship between maternal smoking and metabolic gene polymorphisms of CYP1A1 MspI and GSTT1 with preterm delivery (PTD) as a whole and preterm subgroups. This case–control study included 1,749 multi-ethnic mothers (571 with PTD and 1,178 controls) enrolled at Boston Medical Center. After adjusting covariates, regression analyses were performed to identify individual and joint associations of maternal smoking, two functional variants of CYP1A1 and GSTT1 with PTD. We observed a moderate effect of maternal smoking on PTD (OR = 1.6; 95% CI: 1.1–2.2). We found that compared to non-smoking mothers with low-risk genotypes, there was a significant joint association of maternal smoking, CYP1A1 (Aa/aa) and GSTT1 (absent) genotypes with gestational age (β = −3.37; SE = 0.86; P = 9 × 10⁻⁵) and with PTD (OR = 5.8; 95% CI: 2.0–21.1), respectively. Such joint association was particularly strong in certain preterm subgroups, including spontaneous PTD (OR = 8.3; 95% CI: 2.7–30.6), PTD < 32 weeks (OR = 11.1; 95% CI: 2.9–47.7), and PTD accompanied by histologic chorioamnionitis (OR = 15.6; 95% CI: 4.1–76.7). Similar patterns were observed across ethnic groups. Taken together, maternal smoking significantly increased the risk of PTD among women with high-risk CYP1A1 and GSTT1 genotypes. Such joint associations were strongest among PTD accompanied by histologic chorioamnionitis. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Association between Type 2 Diabetes and CDKN2A/B: a meta-analysis study

Cyclin-dependent kinase inhibitor-2A/B (CDKN2A/B) has been reported as a candidate gene of type 2 diabetes (T2D) based on its chromosomal position and its important role in β-cell function and regeneration. However, studies to date have reported inconsistent findings regarding the association between T2D and CDKN2A/B. To clarify this inconsistence, we conducted a meta-analysis based on alleles and genotypes prevalence of rs10811661 and rs564398 in CDKN2A/B. The PubMed, EMBASE, and Medline databases were systematically reviewed for studies published between January, 2006, and November, 2010. A total of 35 reports were collected, among of them only 16 studies (including 24,407 cases and 33,937 controls) match the inclusion criteria and were selected for the statistical test. In the meta-analysis of published data, our results suggest that the rs10811661 T allele (OR 1.28, 95% CI 1.21–1.36, P < 1 × 10⁻⁵) and TT genotype (OR 1.32, 95% CI 1.22–1.43, P < 1 × 10⁻⁵) of CDKN2A/B were associated with type 2 diabetes respectively, but rs564398 was not (for allele only: OR 0.96, 95% CI 0.88–1.05, P = 0.35). The association between rs10811661 T allele and T2D was observed both in Asia (P < 1 × 10⁻⁴) and Europe ethnicity groups (P = 0.002). This meta-analysis yielded evidence that rs10811661 of CDKN2A/B confers risk for T2D. Larger studies with mixed ethnicity subjects are required to validate our findings.     

Chromium Status and Glucose Tolerance in Saudi Men With and Without Coronary Artery Disease

Chromium deficiency is associated with impaired glucose tolerance (IGT) and dyslipidemia. Hence, the objective of the current study was to investigate chromium status among Saudi men with and without established cardiovascular disease (CVD) and its relationship to glucose tolerance, lipid profile and other established CVD risk factors. We measured serum and urine chromium concentrations, fasted lipid profile, plasma glucose, and serum lipid peroxide in 130 Saudi men with an established history of myocardial infarction and 130 age-matched controls without established CVD. Patients with established CVD had higher serum triglycerides (p < 0.05) and plasma glucose (p < 0.0001) and lower serum and urinary chromium concentrations (p < 0.0001) than controls. Serum chromium was inversely correlated with plasma glucose among cases and controls (r = −0.189, p < 0.05 and r = −0.354, p < 0.00001, respectively). Plasma glucose (OR 1.127, CI 1.0–1.269, p < 0.05), serum chromium (OR 0.99, CI 0.985–0.995, p < 0.0001), and urinary chromium (OR 0.988, CI 0.981–0.995, p < 0.001) were independently associated with the presence of established coronary disease applying this model. While chromium metabolism appears to be altered in individuals with CVD, it is unclear whether chromium supplementation would be effective in CVD prevention among patients with IGT. This would need to be tested in long-term outcome trials.     

Polymorphic markers of some genes associated with multiple sclerosis in the population of Kazakhstan

Associations of DR2 specificity of the DRB1 gene and single-nucleotide polymorphisms of the tumor necrosis factor gene TNFα (−308 G/A), interleukin genes IL-1β (−511 C/T), IL-2 (−475 A/T and −631 G/A), IL-6 (−634 C/G), paraoxanase gene PON1 (M55L, Q192R), and the mitochondrial protein transport gene UCP2 (−866 G/A) with the development of multiple sclerosis (MS) were studied in two main ethnic groups of Kazakhstan (Kazakhs and Russians). An association of DR2 specificity of the DRB1 gene with MS was found in the combined group of Kazakhs, Russians, and offsprings from mixed marriages. No correlation between DR2 specificity and MS was found in the separately examined groups of Kazakhs and Russians. Statistically significant (p < 0.05) differences between the MS patients and healthy individuals were observed in the distribution of the genotypes at site −634 G/C of the IL-6 gene in the Kazakh group, in the allelic frequencies at site −308 A/G in the promoter region of the TNFα gene in the Russian group, and in the frequencies of alleles at the polymorphic Q192R locus of the PON1 gene in the Kazakh group.. No significant differences were revealed in the distribution of the genotypes and in the frequencies of alleles at the polymorphic sites of the genes IL-1β (−511 C/T), IL-2 (−475 A/T and −631 G/A), PON1 (M55L), and UCP2 (−866 G/A).     

Plasminogen activator inhibitor-1 4G/5G promoter polymorphism and PAI-1 plasma levels in young patients with ischemic stroke

The 4G/5G polymorphism in the plasminogen activator inhibitor-1 (PAI-1) gene, has been associated with arterial disease. In this study, we investigated the association of IS in young patients with CRP and PAI-1 levels and frequency of insertion-deletion polymorphism of PAI-1 gene. The plasma levels of PAI-1 and CRP and the frequency of 4G/5G polymorphism were analyzed in 127 Brazilian young patients that presented IS and in 201 healthy and unrelated control subjects. The levels of CRP (P < 0.001) and PAI-1 (P < 0.001) were significantly higher in patients when compared with control group. Only PAI-1 plasma levels were independently associated with risk of IS (OR 3.40; 95% CI 1.49–7.74; P = 0.001) after adjustments for lifestyles covariates. The 4G/4G genotype was significantly more frequent among control subjects as compared to patients (OR 0.41; 95% CI 0.24–0.68; P < 0.001). Although increased PAI-1 plasma levels are associated with development of IS in Brazilian young patients, they are not influenced by the 4G/5G PAI-1 polymorphism.     

No association of monocyte chemoattractant protein-1 −2518 A/G polymorphism with the risk of primary glomerulonephritis in the Polish population

Various studies have indicated that chemokines such as monocyte chemotactic protein-1 (MCP-1) play an important role in the pathogenesis of primary glomerulonephritis (GN) and other glomerular diseases. Moreover, patients with primary GN display aberrant galactosylation of the O-linked carbohydrate moieties of IgA. Therefore, we analysed the distribution of the functional MCP-1 −2518 A > G (rs 1024611) and 1 beta 1,3-galactosyltransferase (C1GalT1) 1365 A > G (rs1047763) polymorphic variants in patients with primary GN (n = 144) and controls (n = 437) in a sample of the Polish population. We did not find a significant difference in the prevalence of the MCP-1 −2518 A > G and C1GalT1 1365 A > G polymorphisms in patients with primary GN and healthy individuals. Odds Ratio (OR) for GN patients with the MCP-1 −2518 GG genotype was 0.869 (95% CI = 0.410–1.840, P = 0.7130), and OR of the −2518 GG and −2518AG genotypes was 1.004 (95% CI = 0.689–1.464, P = 0.9836). OR for C1GalT1 1365AA genotype was 0.484 (95% CI = 0.181–1.293, P = 0.1402) and OR of the 1365AA and 1365AG genotypes was 0.839 (95% CI = 0.573–1.228, P = 0.3651). We also did not observe a difference in the distribution of alleles between patients and controls. The MCP-1 −2518 G allelic OR was 0.976 (95% CI = 0.725–1.314, P = 0.8744). The OR for the C1GalT1 1365A allele was 0.816 (95% CI = 0.596–1.118, P = 0.205). Moreover, there was no significant association between the MCP-1 −2518 A > G and C1GalT1 1365 A > G genotypes with different morphological types of primary GN or clinical manifestations. Our observations indicate that the MCP-1 −2518 A > G and C1GalT1 1365 A > G polymorphisms might not be a risk factor in the incidence of primary GN in the Polish population.     

Polymorphic variants of genes encoding interleukin-6 and fibrinogen, the risk of ischemic stroke and fibrinogen levels

Carriage frequencies of alleles and genotypes of polymorphous locus of -174G>C IL6 (rs1800795) were analyzed in the patients with ischemic stroke (IS) of Russian ethnic descent (200 cases) and in the control group of the same ethnic descent with similar sex and age (140 controls). Significant differences were identified in frequencies of carriage (in homo- or heterozygous form) of allele IL6*-174G (p = 0.0029, OR = 2.9, 95% CI: 1.4-5.8), which can be considered as risk factor for IS and in frequencies of IL6*-174C/C genotype carriage, correspondingly (p = 0.0029, OR = 0.35, 95% CI: 0.17-0.69). After sex stratification of patients and controls similar significant differences were observed only between female patients and controls, after age stratification the difference was observed only for the age group older 60 years. Complex analysis of association of SNP -174G>C IL6 alleles and genotypes carriage in combination with SNP 4266A>G (Thr312Ala) FGA (rs6050) (see symbol) -249C>T FGB (rs1800788) with IS revealed protective combinations IL6*-174C/C + FGA* 4266A (see symbol) IL6*-174C/C + FGB*-249C, which were slightly more significant than single protective genotype IL6*-174C/C associated with IS and their ORs didn't differ substantially from the single genotypes's OR value. At the same time the combinations of alternative allele IL6*-174G with the same FGB*-249C or FGA* 4266A alleles were revealed and their association significance levels as well as OR values were lower than the values for the single risk allele IL6*-174G. In case of the mutual carriage of IL6*-174G allele with FGA*4266A/A, FGB*-249C/C genotypes or with combinations of these alleles/genotypes the "neutralized" effect became stronger. In other words, we observed association of IS with allele/genotype combinations of genes IL6, FGA and FGB, in which IL6 plays key role and FGA and FGB have modulating function. In analysis of association of fibrinogen plasma levels with three analyzed polymorphous loci significant differences were not revealed.     

CYP46 T/C Polymorphism is not Associated with Alzheimer’s Dementia in a Population from Hungary

Multiple genetic and environmental factors regulate the susceptibility to Alzheimer’s disease (AD). Recently, several independent studies have reported that a locus on chromosome 14q32.1, where a gene encoding a cholesterol degrading enzyme of the brain, called 24-hydroxylase (CYP46A1) is located, has been linked with AD. The single nucleotide polymorphism (T/C) in intron 2 of CYP46 gene has been found to confer the risk for AD. The water soluble 24(S)-hydroxysterol is the product of the CYP46A1, and elevated plasma and cerebrospinal fluid hydroxysterol concentrations have been found in AD, reflecting increased brain cholesterol turnover or cellular degradation, due to the neurodegenerative process. A case–control study was performed on 125 AD and 102 age- and gender-matched control subjects (CNT) from Hungary, to test the association of CYP46 T/C and apolipoprotein E (ApoE) gene polymorphisms in AD. The frequency of the CYP46 C allele was similar (χ²=0.647, df=1, P=0.421, exact P=0.466, OR=0.845; 95% CI: 0.561–1.274) in both groups (CNT: 27%; 95% CI: 21.3–33.4; AD 30%; 95% CI: 25.0–36.3). The ApoE ɛ4 allele was significantly over-represented (χ²=11.029, df=2, P=0.004) in the AD population (23.2%; 95% CI: 18.2–29.0) when compared with the CNT (11.3%; 95% CI: 7.4–16.6). The presence or absence of one or two CYP46C alleles together with the ApoE ɛ4 allele did not increase the risk of AD (OR=3.492; 95% CI: 1.401–8.707; P<0.007 and OR=3.714; 95% CI: 1.549–8.908; P<0.003, respectively). Our results indicate that the intron 2 T/C polymorphism of CYP46 gene (neither alone, nor together with the ɛ4 allele) does not increase the susceptibility to late-onset sporadic AD in the Hungarian population.     

Effect of LEPR Gln223Arg polymorphism on breast cancer risk in different ethnic populations: a meta-analysis

Leptin and leptin receptor have been implicated in processes leading to breast cancer initiation and progression. An A to G transition mutation in codon 223, in exon 6 of the leptin receptor gene (LEPR) can result in glutamine to arginine substitution (Gln223Arg). A variety of case–control studies have been published evaluating the association between LEPR Gln223Arg polymorphism and breast cancer. However, published studies have yielded contradictory conclusions. This meta-analysis enrolled eight studies to estimate the overall risk of LEPR Gln223Arg polymorphism associated with breast cancer. The pooled ORs were performed for codominant model (Arg/Arg versus Gln/Gln; Arg/Gln versus Gln/Gln), dominant model (Arg/Arg + Arg/Gln versus Gln/Gln), recessive model (Arg/Arg versus Arg/Gln + Gln/Gln). Overall significantly elevated breast cancer risk was found for recessive model (OR 1.32, 95% CI 1.03–1.69) and for genotype Arg/Gln versus Gln/Gln (OR 1.16, 95% CI 1.01–1.34). In the stratified analysis by ethnicity, significantly increased risks were also found among Africans for genotype Arg/Arg versus Gln/Gln: OR 1.86, 95% CI 1.28–2.71, Arg/Gln versus Gln/Gln: OR 1.48, 95% CI 1.10–1.99, dominant model: OR 1.60, 95% CI 1.21–2.11 and recessive model: OR 1.48, 95% CI 1.07–2.05; for Asians, Arg/Arg versus Gln/Gln: OR 6.79, 95% CI 3.42–13.47 and dominant model: OR 2.03, 95% CI 1.42–2.90. However, no significantly increased risk was found among Europeans for all genetic models. In conclusion, the LEPR 223Arg is a low-penetrant risk for developing breast cancer, especially for black African women.