C-159T Polymorphism Research Articles

Differential Relationships among Facets of Alexithymia and BDNF- and Dopamine-Related Polymorphisms

Alexithymia refers to a cluster of emotion-related deficits such as difficulty attending to and identifying one’s feelings. Although not a diagnosable psychiatric condition, alexithymia is considered a personality risk factor for multiple pathologies, including somatoform, substance use, eating, and mood disorders. Evidence suggests heritability, but few studies have examined the influence of specific genes on alexithymic traits. Candidate genes explored thus far include those involved in modulation of brain-derived neurotrophic factor (BDNF) and dopamine, two neurotransmitters whose functions have been implicated in human emotion processing. This study investigated the relationship between the C270T polymorphism of the BDNF gene, facets of alexithymia, and possible interactions with the COMT, DAT1, and ANKK1 genes in a sample of 130 healthy adults. Given the multidimensionality of the alexithymia construct and its overlap with the related constructs of emotional intelligence and mood awareness, we used principal components analysis to derive Clarity of Emotion and Attention to Emotion as specific facets of alexithymia. Results showed that the C270T C/C genotype group had lower Clarity of Emotion scores relative to the C/T genotype group, even after covarying for COMT, DAT1, and ANKK1 genotypes. Dopamine-related genes had no association with alexithymia dimensions, nor did they interact with the C270T polymorphism to predict Clarity of Emotion. Although the molecular mechanisms by which this polymorphism influences BDNF are unknown, this study suggests a role for BDNF in modulating aspects of alexithymia. We discuss these results in the context of BDNF’s trophic effects in the nervous system.

Association Study on IL4, IL13 and IL4RA Polymorphisms in Mite-Sensitized Persistent Allergic Rhinitis in a Chinese Population

BackgroundThe IL4, IL13, and IL4 receptor α chain (IL4RA) genes are candidate genes for atopic diseases. We hypothesized that the polymorphisms in these genes are associated with persistent allergic rhinitis (PER).ObjectiveTo investigate the association of the potential functional polymorphisms in IL4, IL13, and IL4RA with PER induced by house dust mites in a Chinese population.MethodsUsing the TaqMan method, we genotyped six single nucleotide polymorphisms (SNPs) including C-590T in IL4, C-1055T and Arg130Gln in IL13, and Ile50Val, Ser478Pro and Gln551Arg in IL4RA, in a case-control study of 265 patients with PER and 275 healthy controls.ResultsWe found that the CT/CC genotypes in IL4 C-590T were associated with a significantly decreased risk of mite-sensitized PER [adjusted odds ratio (OR) = 0.64, 95% confidence interval (CI) 0.45–0.92], compared to the TT genotype. Furthermore, PER patients with CT/CC genotypes had significantly lower serum levels of total IgE than those with TT genotype (P = 0.001). However, there was no significant association of the IL13 and IL4RA polymorphisms with mite-sensitized PER (P>0.05).ConclusionsOur results suggest that the C-590T polymorphism in IL4 may contribute to the susceptibility to mite-sensitized PER in a Chinese population.

Associations of IL-4, IL-4R, and IL-13 gene polymorphisms in coal workers' pneumoconiosis in China: a case-control study.

BackgroundThe IL-4, IL-4 receptor (IL4R), and IL-13 genes are crucial immune factors and may influence the course of various diseases. In the present study, we investigated the association between the potential functional polymorphisms in IL-4, IL-4R, and IL-13 and coal workers' pneumoconiosis (CWP) risk in a Chinese population.MethodsSix polymorphisms (C-590T in IL-4, Ile50Val, Ser478Pro, and Gln551Arg in IL-4R, C-1055T and Arg130Gln in IL-13) were genotyped and analyzed in a case-control study of 556 CWP and 541 control subjects.ResultsOur results revealed that the IL-4 CT/CC genotypes were associated with a significantly decreased risk of CWP (odds ratio (OR) = 0.74, 95% confidence interval (CI) = 0.58–0.95), compared with the TT genotype, particularly among subgroups of age <65 years (OR = 0.68, 95%CI = 0.46–0.99) and dust exposure years ≥26 years (OR = 0.69, 95%CI = 0.50–0.94). Moreover, the polymorphism was significantly associated with risk of CWP patients with stage I. In addition, a combined effect was observed in a dose-dependent manner with increasing numbers of risk variant alleles (P trend = 0.023), and individuals with 11–12 risk alleles had a 47% higher risk of CWP than those with 0–8 risk alleles (OR = 1.47, 95% CI = 1.05–2.05).ConclusionsOur results suggest that the IL-4 C-590T polymorphism is involved in the etiology of CWP and susceptibility to this disease. Larger studies are warranted to validate our findings.

Association between brain‐derived neurotrophic factor (BDNF) gene polymorphisms and executive function in Japanese patients with Alzheimer's disease

To address the functional roles of genetic polymorphisms of brain-derived neurotrophic factor (BDNF) in Alzheimer's disease (AD) from a neuropsychological aspect, we used a cross-sectional study design to investigate the association between novel single nucleotide polymorphisms (SNPs) of the BDNF gene (Val66Met (G196A) and C270T) and the Frontal Assessment Battery (FAB) score, which reflects executive function as a non-memory cognitive impairment. One hundred and sixty-nine outpatients with AD or amnestic mild cognitive impairment (A-MCI) were recruited to the study and divided into three genotypic groups for each representative BDNF functional polymorphism as follows: (i) Val66Met (G196A): G/G (n = 45), G/A (n = 104), and A/A (n = 20); and (ii) C270T: C/C (n = 160), C/T (n = 9), and T/T (n = 0). Then, age, sex ratio, duration of illness (months), education years, Mini-Mental State Examination (MMSE) score, behavioral pathology in Alzheimer disease (Behave-AD) score, Clinical Dementia Rating (CDR) ratio, and total and subtest FAB scores were compared between the genotypic groups for each SNP. Significant differences were found in the total (P < 0.01) and subtest (conflicting instructions and prehension behavior; P < 0.01) FAB scores between the C270T polymorphism groups (C/C and C/T), but not among the G196A polymorphism groups. However, no significant differences in age, sex ratio, duration of illness (months), education years, Behave-AD score, CDR ratio, or MMSE score (reflecting attention and memory function) were found between the individual polymorphism genotypes (G196A and C270T). Of the known BDNF polymorphisms, the C270T SNP may influence executive dysfunction as a non-memory cognitive impairment in Japanese patients with AD.

Association between circulating interleukin-1 beta (IL-1β) levels and IL-1β C–511T polymorphism with cervical cancer risk in Egyptian women

Cancer cervix is one of the leading causes of cancer-related mortality among women worldwide. It is believed that the host genetic factors such as inflammation-induced cytokines may play a role in cervical carcinogenesis. The interleukin-1β (IL-1β) gene contains several single nucleotide polymorphisms. One of them, C-511T, which in the promoter region has been associated with increased IL-1β production and with increased risk of developing cancers. We assessed the association between the IL-1β C-511T polymorphism and cervical cancer risk in a case-control study among 100 histopathologically confirmed Egyptian women with cervical cancer and 50 age-matched, cervical cytology negative, healthy controls by polymerase chain reaction-restriction fragment length polymorphism. Plasma levels of IL-1β were assayed by enzyme-linked immunosorbent assay. There was significant increase in the mean plasma IL-1β level in cervical cancer cases (43.40 ± 25.95 pg/ml) when compared with controls (30.51 ± 18.28 pg/ml, P = 0.002). The plasma levels above the 75th percentile of controls (IL-1β ≥ 45.74 pg/ml) were significantly associated with a 2.49-fold increased risk of cervical cancer. The significant increase in IL-1β concentration in cervical cancer cases was observed only among cervical cancer cases carrying C-511T variant genotypes. T/T genotype of IL-1β polymorphism was significantly higher in cervical cancer cases compared with controls (57 vs. 38%; OR = 2.16; P = 0.028) and the T allele carriage was significantly associated with cervical cancer risk (OR = 2.00, 95% CI = 1.19-3.38, and P = 0.008). In conclusion, plasma IL-1β level and IL-1β C-511T polymorphism may be considered as candidate biomarkers for cervical cancer in Egyptian women.

Lack of effect of the CD14 promoter gene C-159T polymorphism on nutritional status parameters in hemodialysis patients

SummaryBackgroundCD14 is a membrane glycoprotein that acts as a co-receptor for the detection of bacterial lipopolysaccharide (LPS). Mutual interaction between CD14 and LPS plays an important role in the innate immune system. Increased serum soluble CD14 levels have been described in hemodialysis (HD) patients, and linked to increased mortality risk, inflammation and protein-energy wasting. The expression of CD14 may be influenced by CD14 promoter gene C-159T polymorphism.This study aimed to clarify the possible association between CD14 promoter gene C-159T polymorphism and nutritional status in hemodialysis patients.Material/MethodsThe study population consisted of 185 (104 males; 81 females) long-term HD patients treated in 5 dialysis centers. The control group consisted of 112 apparently healthy volunteers (32 males and 80 females). Nutritional status was assessed using a modified SGA scale, and anthropometric methods (BMI, WHR, waist, hip and mid-arm circumferences, biceps, triceps, subocular and subscapular skinfolds). Biochemical parameters evaluated included: CRP, albumin, creatinine, urea, cholesterol, triglycerides and TIBC. CD14 promoter gene C-159T polymorphism was determined by restriction fragment length polymorphism, after digestion of the PCR product with Hae III restriction endonuclease.ResultsGenotype and allele frequencies were similar to controls and compliant with Hardy-Weinberg equilibrium. No between-group differences were detected in measured variables with the exception of lower triglyceride levels in carriers of C allele in comparison to TT genotype.ConclusionsCD14 promoter gene C-159T polymorphism does not seem to be associated with nutritional status parameters in HD patients. It does seem, however, to influence triglyceride blood levels.

258 C(-260)T polymorphism in the promoter of CD 14 gene is not associated with myocardial infarction in the tunisian population

Recent finding suggest that inflammation plays a role in atherosclerosis and its acute complications. Several known mechanisms may play at least a partial role in this process. One of the most likely mechanisms involves lipopolysaccharide (LPS) and its receptor, CD14. The C(-260)T single nucleotide polymorphism in the promoter region of the CD14 receptor gene has been reported to be associated with a higher risk of MI. Others studies, however, have not corroborated these findings. Considering the contradictory results, the aim of the present study was to investigate the possible association between the CD14 C(-260)T polymorphism and the risk of MI in the Tunisian population. A total of 333 Tunisian patients with MI and 345 healthy controls were included in the study. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The frequency of TT homozygous genotype for the CD14 C(-260)T polymorphism was 24.9% in MI patients and 24.0% in the control group. However, the genotype distribution and allele frequencies were not significantly different between MI and controls subjects. Moreover, the odds ratio for MI associated with the T allele failed to reach statistical significance (OR = 1.08; 95% CI: 0.86 – 1.34; P = NS). These results do not support the hypothesis that the C-260T polymorphism of CD14 gene contributes to the genetic susceptibility to MI in the Tunisian population studied.

The effect of CD14 C159T polymorphism on in vitro IgE synthesis and cytokine production by PBMC from children with asthma

Even though the genotype at the promoter region of the CD14 molecule is known to affect the atopic phenotypes, the cellular and molecular basis of this association is largely unknown. To investigate the effect of lipopolysaccharide (LPS) on IgE production and cytokine profile by peripheral blood mononuclear cells (PBMC) obtained from asthmatic children with the TT and the CC genotypes at position -159 of the CD14 gene. Peripheral blood mononuclear cells from asthmatic children with alternative genotypes at CD14 C159T locus were stimulated with 2 and 200 ng/ml LPS in vitro. The IgE, IgG and, IgM response was determined by ELISA and Ig έ-germline, IgG, and IgM transcription by real-time PCR. A cluster of cytokines was measured by cytometric bead array. Asthmatic children with the TT genotype but not those with the CC genotype responded with increased IgE synthesis and germline transcription to LPS stimulation. There were no genotype-related differences in IgG and IgM. TT but not the CC genotype was associated with significantly increased interleukin (IL)-4/IL-12 and IL-4/interferon-gamma (IFN-γ) ratios in the culture supernatant. There were no genotype-related differences in IL-1β, IL-7, IL-10, IL-13, IL-17A, granulocyte colony stimulating factor, granulocyte macrophage colony stimulating factor, monocyte chemotactic protein, and tumor necrosis factor alpha. Peripheral blood mononuclear cells from asthmatic children with the TT genotype at position -159 of the CD14 gene make more IgE than those with the CC genotype following LPS stimulation because of increased germline transcription and have an augmented Th2 cytokine profile.

Brain‐derived neurotrophic factor gene polymorphisms and serum levels in Chinese atopic dermatitis patients

Brain-derived neurotrophic factor (BDNF) plays an important role in the pathogenesis of atopic dermatitis (AD). Whether BDNF gene polymorphisms are associated with Chinese AD remains totally unknown. The aim is to determine if BDNF gene C270T and G196A polymorphisms are associated with Chinese AD, and analyse the clinical relevance of BDNF gene polymorphisms and BDNF serum levels. Methods We conducted a case-control association analysis (160 patients and 169 controls) in Northern Chinese subjects. Genotyping was performed by restriction fragment length polymorphism, and serum levels of BDNF were measured using enzyme-linked immunosorbent assay. For C270T, there were significant differences in C/T genotype distribution (P = 0.003) and T allele frequencies (P = 0.004) between AD patients and controls in the whole dataset. Higher C/T genotype frequencies were found in male AD (10.6% vs. 1.1%, P = 0.018) and in intrinsic AD (IAD; 15.79% vs. 2.91%, P = 0.008). No association between G196A polymorphism and AD was observed in the whole cohort, while A allele was much more frequent in AD patients with atopy in first-degree relatives (65.8% vs. 34.2%, P = 0.038). Serum BDNF levels were correlated with IAD severity as measured by Scoring Atopic Dermatitis index (r = 0.576, P < 0.001). T allele in C270T may be a risk factor for AD, especially in IAD and male AD. A allele in G196A may be a risk factor in AD patients with atopy in first-degree relatives. Serum BDNF levels were correlated with the severity of IAD.

CD14 C-159T and Toll-Like Receptor 4 Asp299Gly Polymorphisms in Surviving Meningococcal Disease Patients

BackgroundCarriage of Neisseria meningitidis occurs approximately in 10% of the population, onset of invasive meningococcal disease (IMD) cannot be predicted and differs between ages. It remains unclear, which host factors determine invasion of the bloodstream by the bacteria. Innate immunity has a very important role in the first recognition of invading pathogens. The functional single nucleotide polymorphisms (SNPs) CD14 C-159T and toll-like receptor 4 (TLR4) Asp299Gly have been associated with the risk of gram-negative infections. However, their role in development of IMD still remains unclear. Our aim was to investigate the influence of CD14 C-159T and TLR4 Asp299Gly polymorphisms on the risk of IMD.Methodology/Principal FindingsIt was a retrospective case control study. Surviving Austrian meningococcal disease patients were enrolled by sending buccal swabs for DNA analysis. 185 cases with a proven meningococcal infection and 770 healthy controls were enrolled. In surviving meningococcal disease patients DNA analysis of CD14 C-159T and TLR 4 Asp299Gly polymorphisms was performed, as they are part of the innate immune response to bacterial determinants. CD14 C-159T and TLR4 Asp299Gly SNPs were not significantly associated with the presence of IMD when compared to healthy controls. The odds ratio for CD14 C-159T SNP was 1.14 (95% confidence interval (CI) 0.91–1.43; p = 0.266). In TLR4 Asp 299 Gly SNP the odds ratio was 0.78 (CI 0.47–1.43; p = 0.359).Conclusion/SignificanceWe could not observe a significant influence of CD14 C-159T and TLR4 Asp299Gly polymorphisms on the risk of developing IMD in surviving meningococcal disease patients. To our knowledge, this is the first study investigating the influence of the CD14 C-159T SNP on the susceptibility to IMD.

Polyacrylamide Gel-based Microarray: A Novel Method Applied to the Association Study Between the Polymorphisms of BDNF Gene and Autism

Single nucleotide polymorphisms (SNPs) are important markers which can be used in the association study for searching for associated genes of complex diseases. High-throughput methods in a large number of samples are needed for SNP genotyping. In this study, we applied polyacrylamide gel-based microarray combined with universal dual-color hybridization for trios-based associative study of BDNF polymorphisms with autism in Chinese. All four SNPs in both patients and their parents could be analyzed quickly and correctly. In single SNP TDT analysis, C270T showed preferential transmission of the T allele compared to the C allele (TDT p < 0.001) in autism. In haplotype TDT analysis, C270T polymorphism also existed in the haplotype combination which showed significant association (TDT p < 0.05). These results suggest a potential association between BDNF and autism in the Chinese population. The study also show that the polyacrylamide gel-based microarray combined with universal dual-color detectors is a rapid, simple, high-throughput method for SNPs genotyping, and can be very effective and cost effective in association study of susceptible gene with disorders in large samples.

Analysis of 14 genetic polymorphisms for risk factors in Malaysian essential hypertension with or without type 2 diabetes mellitus subjects

Objectives The objective of this study was to determine the association of insertion/deletion (I/D), G2350A and T3892C polymorphisms of angiotensin converting enzyme (ACE) gene, A20C and A6G polymorphism of angiotensinogen (AGT) gene, BglI and MboI polymorphisms of renin gene, I/D of alpha 2B adrenoceptor gene, Gly460Trp of aldosterone synthase gene, Lys173Arg of adducin gene, A6244G polymorphism of the insulin receptor gene, S477X polymorphism of the lipoprotein lipase gene, C511T polymorphism of the interleukin gene and C825T polymorphism of the G protein beta 3 subunit (GNβ3) gene in essential hypertension (EHT) with or without type 2 diabetes mellitus (T2DM) of Malaysian subjects. Methods This cross-sectional study includes 70 EHT without T2DM, 65 EHT with T2DM and 75 unrelated healthy control subjects. Genomic DNA was extracted from the peripheral blood. The polymerase chain reaction (PCR)-restriction fragment length polymorphism, mutagenically PCR and the hot-start PCR methods were carried out to detect the genotypes of the various genetic polymorphisms. All the PCR products and the restricted fragments were resolved electrophoretically on agarose and polyacrylamide gels. Statistical analyses was done using SPPS version 14.0. Results Among the 14 genetic polymorphisms, only I/D and G2350A polymorphism of ACE gene, I/D polymorphism of alpha adrenoceptor gene and A6G variant of AGT gene differed significantly (p 0.05) when compared to control subjects. Conclusions The alleles of I/D and G2350A polymorphisms of ACE, A6G of AGT and I/D of alpha 2B adrenoceptor genes can be considered as possible genetic markers or predisposing risk factors for EHT with or without T2DM in Malaysian subjects.

Association of C-159T polymorphism in promoter region of CD14 with diabetic nephropathy

Objective To investigate the distribution of CD14 promoter gene C-159T polymorphsim in patients with type 2 diabetes mellitus(T2DM)and to analyze the association of CDI4 polymorphisms with diabetic nephropathy (DN). Methods Genotypes of CD14 were typed in 308 T2DM patients and 145 normal controls by polymerase chain reaction restriction fragment length polymorphism. Results (1)The distribution of CD14 promoter gene C-159T polymorphsim revealed no significant difference between normal control group and T2DM group(P>0.05). The distributions between CC genotype and CT+TT genotypes existed statistically significant difference in CD14-159 between two subgroups with and without diabetic nephropathy (P<0.05). (2)At 10 and 20 years after the onset of DM, 13.3% and 23.4% of the patients developed into DN respectirely. CC genotype had higher risk than CT+TT genotypes to develop into DN. Conclusion The distribution of CD14 promoter gene C -159T polymorphism has no relation with T2DM. The CC genotype of the C-159T polymorphism of CD14 gene is a risk factor for diabetic nephropathy. Key words: CD14 promoter; Diabetic nephropathies; Polymorphism, single nucleotide; Lipopolysaccharidereceptor

Allelic Polymorphism of Cytokine Genes during Pulmonary Tuberculosis

Modern immunological and molecular genetic studies showed that tuberculosis is accompanied by an imbalance in the production of immunoregulatory cytokines by mononuclear leukocytes. T allele and homozygous TT genotype of T-330G polymorphism in the IL2 gene, T allele and TT genotype of C-590T polymorphism in the IL4 gene, and CC genotype of A-1188C polymorphism in the IL12B gene are immunogenetic factors that have protective activity against susceptibility to pulmonary tuberculosis. Susceptibility to tuberculous infection is associated with A1A2 genotype of the polymorphic region +3953 A1/A2 in the IL1B gene; G allele and TG and GG genotypes of T-330G polymorphism in the IL2 gene; C allele and CC and CT genotypes of C-590T polymorphism in the IL4 gene; and AC genotype of the polymorphic region A-1188C in the IL12 gene.

The Association with the −159C/T Polymorphism in the Promoter Region of the CD14 Gene and Juvenile Idiopathic Arthritis in a Chinese Han Population

Juvenile idiopathic arthritis (JIA) is generally considered to be caused by interaction of genetic and environmental factors. We investigated the association of a C-to-T transition in the promoter region of the CD14 gene on chromosome 5q31.1 and JIA in a Chinese Han population. One hundred sixty-three children with JIA and 281 healthy children (age- and sex-matched to JIA group) were studied. Polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) was used for analysis of the genotypes. (Trial registration number ChiCTR-CCC-00000312.) CD14 promoter-159 genotype frequencies of CC, CT, and TT were 11.48%, 49.18%, and 39.34%, respectively, in the systemic onset JIA group; 21.62%, 43.24%, and 35.14%, in the polyarticular JIA group; 16.67%, 50%, and 33.33%, in the oligoarticular JIA group; 6.9%, 75.86%, and 17.24%, in the group with other types of JIA; and 37.01%, 46.98%, and 16.01%, in the control group. Genotype frequency and allele frequency distribution were in accord with Hardy-Weinberg equilibrium. There were statistically significant differences in frequencies of genotype and allele in CD14 C-159T polymorphism between JIA group and control group (genotype: chi-squared = 33.168, p < 0.05, CT vs CC, OR 2.946, 95% CI 1.739-4.990; TT vs CC, OR 5.426, 95% CI 2.977-9.891. Allele: chi-squared = 33.168, p < 0.05, T vs C, OR 2.251, 95% CI 1.704-2.973). The T allele frequencies of boys and girls were significantly higher than those in the control group (p < 0.001 of both). CD14 gene promoter C-159T polymorphism is significantly correlated with JIA in the Chinese Han population. The T allele of the C-159T polymorphism of CD14 gene may be a genetic risk factor for JIA.

Role of non‐HLA genetic variants in end‐stage renal disease

Cytokines and intercellular adhesion molecule (ICAM) play a crucial role in the pathogenesis of primary kidney disease and progression to end-stage renal disease (ESRD). Cytokine secretion is reported to be dependent on the single nucleotide polymorphisms located in the cytokine genes. The role of different polymorphisms in cytokines and ICAM genes as probable susceptibility factors for ESRD has been explored in the present study. The study was conducted on 258 ESRD patients and on ethnically matched 569 controls. Individuals were genotyped for interleukin (IL)-6 (G174C), IL-4 (C590T), tumor necrosis factor-alpha (TNF-alpha) (-G308A and -G238A) and ICAM-1 (A469G) gene polymorphisms using standard polymerase chain reaction-restriction fragment length polymorphism-based method. We observed significant difference in the genotype frequencies of the TNF-alpha-308AA [P = 0.001; odds ratios (OR) = 7.61, 95% confidence intervals (CI) = 2.1-27.9] and TNF-alpha-238AA (P = 0.001; OR = 5.8, 95% CI = 2.2-15.1). Furthermore, C allele of IL-6 -G174C and G allele of ICAM-1 A469G were significantly different in ESRD patients when compared with controls (P = 0.0001; OR = 5.5, 95% CI = 3.9-7.7 and P < 0.0001; OR = 3.8, 95% CI = 3.1-4.7). For the IL-4 C590T polymorphism, although the homozygous mutant genotype (TT) was not found to be significantly associated with ESRD, a statistically significant association with T allele (P = 0.008) was observed. Furthermore, combined analysis showed a higher risk in ESRD patients with high IL-4- and low IL-6-producing genotypes, low IL-4- and low IL-6-producing genotypes and high-producing genotype of TNF-alpha (308 and 238) with the increased risk of 6.47-, 3.7- and 3.3-fold, respectively. Our results suggest that IL-6, IL-4, TNF-alpha and ICAM gene polymorphisms are implicated in ESRD.

Association Study between BDNF Gene Polymorphisms and Autism by Three-Dimensional Gel-Based Microarray

Single nucleotide polymorphisms (SNPs) are important markers which can be used in association studies searching for susceptible genes of complex diseases. High-throughput methods are needed for SNP genotyping in a large number of samples. In this study, we applied polyacrylamide gel-based microarray combined with dual-color hybridization for association study of four BDNF polymorphisms with autism. All the SNPs in both patients and controls could be analyzed quickly and correctly. Among four SNPs, only C270T polymorphism showed significant differences in the frequency of the allele (χ2 = 7.809, p = 0.005) and genotype (χ2 = 7.800, p = 0.020). In the haplotype association analysis, there was significant difference in global haplotype distribution between the groups (χ2 = 28.19, p = 3.44e-005). We suggest that BDNF has a possible role in the pathogenesis of autism. The study also show that the polyacrylamide gel-based microarray combined with dual-color hybridization is a rapid, simple and high-throughput method for SNPs genotyping, and can be used for association study of susceptible gene with disorders in large samples.

CD14 C260T promoter polymorphism and the risk of cerebrovascular diseases: a meta-analysis

Cerebrovascular diseases (CVD) are dysfunctions of the brain, resulting from diseases of blood vessels supplying the brain. Atherosclerosis is one of the major underlying causes of CVD, in which inflammation plays a crucial role. One of the inflammatory mechanisms contributing to atherogenesis is the activation of monocytes and macrophages, which could be mediated by the bacterial endotoxin lipopolysaccharide (LPS) via its receptor CD14. The C260T (rs2569190) single-nucleotide polymorphism (SNP) in the promoter region of the CD14 gene was implicated in CVD. To assess the role of this SNP in CVD, a comprehensive meta-analysis of the available genetic data was conducted. All the case-control association studies evaluating the role of CD14 C260T in CVD were identified. Of these, 7 studies (comprising a total of 1488 patients and 1600 control subjects) were included in this meta-analysis. To measure the strength of genetic association for the gene variant, the odds ratios (ORs) were calculated using both fixed and random effects for comparisons of the alleles, the genotypes, and the dominant and recessive genotype models. The results showed there was no significant association between the T allele of C260T and the risk of CVD under the fixed effects model, OR = 0.99 (95% CI (0.89, 1.09)), P = 0.84; or the random effects model, OR = 0.99 (95% CI (0.88, 1.11)), P = 0.83. Similar results were obtained for the homozygotes and the dominant and recessive models. In conclusion, the results of this meta-analysis suggest the CD14 C260T polymorphism is not a risk factor for CVD. However, more studies in ethnically varied populations are needed to evaluate in a reliable manner the role of this SNP in CVD susceptibility.

Associação entre os polimorfismos dos genes MBL2, TGF-β1 e CD14 com a gravidade da doença pulmonar na fibrose cística

To identify associations between genetic polymorphisms (in the MBL2, TGF-beta1 and CD14 genes) and the severity of the lung disease in patients with cystic fibrosis (CF), as well as between the presence of DeltaF508 alleles and lung disease severity in such patients. This was a cross-sectional cohort study, based on clinical and laboratory data, involving 105 patients with CF treated at a university hospital in the 2005-2006 period. We included 202 healthy blood donors as controls for the determination of TGF-beta1 and CD14 gene polymorphisms. Polymorphisms in the MBL2 and TGF-beta1 genes at codon 10, position +869, were genotyped using the allele-specific PCR technique. The C-159T polymorphism in the CD14 gene was genotyped using PCR and enzymatic digestion. Of the 105 CF patients evaluated, 67 presented with severe lung disease according to the Shwachman score. The MBL2 gene polymorphisms were not associated with disease severity in the CF patients. Analysis of the T869C polymorphism in the TGF-beta1 gene showed an association only between TC heterozygotes and mild pulmonary disease. Although patients presenting the TT genotype of the C159T polymorphism in the CD14 gene predominated, there was no significant difference regarding lung disease severity. There was an association between the TC genotype of the T869C polymorphism (TGF-beta1) and mild pulmonary disease in CF patients. In the CD14 gene, the TT genotype seems to be a risk factor for pulmonary disease but is not a modulator of severity. We found no association between being a DeltaF508 homozygote and presenting severe lung disease.

Endotoxin receptor CD14 gene variants and histological features in chronic HCV infection

To analyze the correlation between CD14 rs2569190/C-159T single nucleotide polymorphism (SNP) and disease progression in chronic hepatitis C. Liver biopsy specimens from a total of 137 and 349 patients with chronic hepatitis C were separately evaluated with respect to necroinflammatory activity (grading) and architectural changes (staging). In one group, further histological lesions characteristic for hepatitis C, hepatitis C virus subtypes, and biochemical parameters of liver disease were also investigated. Samples of genomic DNA were genotyped for the respective SNP by 5'-nuclease assays using fluorescent dye-labeled allele-specific probes. Genotype distribution did not deviate from the Hardy-Weinberg equilibrium. In the first group, patients homozygous for the variant allele T were found to be younger than C allele carriers (39.6 +/- 12.5 vs 45.7 +/- 11.5, P = 0.008). Among the histological lesions studied, portal lymphoid aggregates were more frequently observed among TT homozygotes than among C carriers (21/37 vs 32/100, P = 0.008). The presence of portal lymphoid aggregates was closely correlated with hepatic inflammation (P = 0.003) and with bile duct damage (P < 0.001). The degree of fibrosis, in contrast, was not found to be related to the CD14 gene C-159T polymorphism. The data suggest a possible relationship between CD14 C-159T polymorphism and the formation of portal lymphoid aggregates, but not liver fibrosis progression in chronic hepatitis C.