Association of the -159 C --> T polymorphism in the CD14 promoter with variations in serum lipoproteins in healthy subjects.

The CD14-159 C --> T polymorphism, a single nucleotide polymorphism (SNP) at position -159 in the promoter region of the gene encoding the pattern recognition receptor CD14, has been associated with elevated plasma concentrations of soluble CD14, lowered serum immunoglobulin E, increased risk for myocardial infarction, and decreased risk for allergy and asthma. In the present study, the CD14-159 C --> T polymorphism has been investigated in order to determine its frequency and association with proinflammatory variables and lipid profile traits of 117 volunteers. The frequency of the CD14 promoter genotype as determined by polymerase chain reaction amplification-restriction fragment length polymorphism analysis was 35.0% (CC), 44.4% (CT), and 20.5% (TT), and the T allele frequency was 42.7%. Compared with the other genotypes, notably CC homozygotes, TT homozygotes were associated with lower total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B-100 (P < 0.01) concentrations in serum. However, no association was found between the investigated SNP and inflammatory mediators such as fibrinogen, interleukin-6, tumor necrosis factor-alpha, tissue factor, C-reactive protein, plasminogen activator inhibitor-1, leukotriene B4, or thromboxane B2. In conclusion, the CD14-159 C --> T polymorphism may be an important genetic trait, related to the ability of CD14 to bind and transport lipids, such as cholesterol.     

Polymorphisms in the CD14 gene associated with pulmonary function in farmers

RATIONALE AND OBJECTIVES: Farmers experience airway obstruction, which may be attributable in part to endotoxin inhalation. CD14 is a receptor for endotoxin. MATERIALS AND METHODS: Based on our findings of increased circulating CD14 associated with the CD14/-159 T allele, we hypothesized that carriers of this allele would have decreased lung function among endotoxin-exposed individuals. CD14/-159TT farmers (n = 19) had significantly lower lung function as measured by FEV1 (p = 0.028) and mean forced expiratory flow during the middle half of the FVC (FEF25-75) (p = 0.05) compared with farmers with the C allele (n = 78). Also, farmers with the CD14/-1619GG genotype (n =11) were associated with lower lung function (FEV1, p = 0.008; FEF25-75, p = 0.009) compared with farmers with the A allele (n = 86). RESULTS: No association between CD14/-550 and lung function was observed (FEV1, p = 0.32; FEF25-75, p = 0.11). Increased prevalence of wheezing was reported in farmers homozygous for CD14/-159T (p = 0.013) or CD14/-1619G (p = 0.019) compared with farmers with the CC or AA genotype, respectively. No association was found between TLR4/Asp299Gly and lung function or wheeze. CONCLUSION: We conclude that the CD14/-159 or CD14/-1619 loci may play a role in modulating lung function and wheeze among agricultural workers.     

Association of the -159C/T polymorphism of the endotoxin receptor (CD14) with carotid artery disease and cardiovascular mortality in dialysis patients

BACKGROUND: Atherosclerosis is a major problem in end-stage renal disease (ESRD) patients treated by hemodialysis and the prevalence of carotid artery disease is much higher in this group than in the general population. Repeated exposure to cytokine-inducing material, derived from dialysate, may induce a chronic inflammatory state, that could contribute to the atherosclerotic process. Endotoxin is mainly cleared from plasma by the sCD14, the soluble form of the endotoxin receptor CD14. The levels of sCD14 are associated with a polymorphism, -159 C/T, of the CD14 gene. METHODS AND RESULTS: We determined the genotype for the -159 C/T polymorphism in 158 haemodialysis patients and 168 healthy controls. In patients we investigated the association between the CD14 polymorphism and carotid artery disease. With a prospective follow-up study we assessed whether the CD14 polymorphism shows any relationship with cardiovascular mortality. The polymorphic frequency was comparable between patients and controls. In patients, we found a significant difference in the prevalence of carotid artery disease between groups divided by genotype: CC 87.0%, CT 71.7%, TT 48.9% (p = 0.0093). In dialysis patients with hypertension the CC polymorphism was associated with an increased cardiovascular mortality. CONCLUSIONS: These results demonstrate an association between the -159 C/T polymorphism of the CD14 gene and carotid artery disease in dialysis patients. We hypothesize that the low plasma clearance of endotoxin associated with the CC genotype facilitates the atherogenic action of endotoxin-derived cytokines in haemodialysis patients.     

Acute asthma in children: Relationships among CD14 and CC16 genotypes, plasma levels, and severity

RATIONALE: The majority of previous studies investigating asthma genetics have focused on cohorts with stable disease and have not defined mechanisms important during acute asthma. CD14 and CC16 each play a key role in biologically important inflammatory pathways and the gene of each has a functional promoter-region polymorphism. OBJECTIVES: This study was designed to determine the influence of these polymorphisms on plasma levels of their products and clinical disease during acute asthma. We hypothesized that genotype-related differences in CD14 and CC16 production would be more marked during acute asthma and related to disease severity. METHODS: We studied 148 children on presentation with acute asthma and again in convalescence. CD14 C-159T and CC16 A38G genotypes were determined, and plasma levels of soluble CD14 (sCD14) and CC16 were measured at both times. MEASUREMENTS AND MAIN RESULTS: During acute asthma, plasma sCD14 levels were higher for the whole group (p = 0.003), but increases were only in subjects with CD14 -159TT (p = 0.003) and -159CT (p = 0.004), and not in those with -159CC. Plasma CC16 levels were also elevated acutely for the whole group (p = 0.013), but only in those with CC16 38GG (p = 0.043) and 38AG (p = 0.014), and not in those with CC16 38AA. Subjects with CD14 -159CC and CC16 38AA were more likely to have moderate or severe acute asthma. CONCLUSIONS: Plasma levels of sCD14 and CC16 were higher during acute asthma in the subjects. Those with CD14 -159CC and CC16 38AA had no change in sCD14 and CC16 levels and more severe asthma.     

Gene by environment interaction: the -159C/T polymorphism in the promoter region of the CD14 gene modifies the effect of alcohol consumption on serum IgE levels

BACKGROUND: Serum IgE is increased in heavy drinkers. Endotoxin mediates most of the immunological alterations associated with heavy drinking. The -159C/T polymorphism in the promoter region of the gene encoding CD14 (an endotoxin receptor) is associated with serum IgE levels in different populations. AIM: To investigate the possible interaction between alcohol intake and the -159C/T polymorphism in the promoter region of the CD14 gene for serum IgE levels. METHODS: A total of 415 individuals (51.6% males, median age 50 years, range 18-92 years) were studied. A total of 140 individuals were alcohol abstainers, 112 were moderate drinkers (1-280 g/week), and 163 were heavy drinkers (>280 g/week). Main determinations included the CD14/-159C/T genotype, a panel of skin prick tests, total serum IgE, and specific serum IgE against common aeroallergens (Phadiatop test). RESULTS: Heavy drinking was associated with increased total serum IgE values and with positive specific serum IgE to common aeroallergens, but the association was stronger in carriers of the CD14/-159C allele (either CC homozygotes or CT heterozygotes) than in CD14/-159TT homozygotes. Both additive and multiplicative interactions between heavy drinking and the CD14/-159C allele for total and specific serum IgE values was still present after adjusting for potential confounders. Neither alcohol consumption nor the CD14/-159 genotype was associated with skin prick test positivity. CONCLUSIONS: The CD14/-159C/T polymorphism modifies the effect of alcohol consumption on serum IgE levels.     

Promoter polymorphism of the CD14 endotoxin receptor gene as a risk factor for alcoholic liver disease

Twin concordance studies indicate that genetic factors influence the individual susceptibility for alcoholic liver disease (ALD). Both clinical and experimental data suggest that Kupffer cell activation by gut-derived endotoxins and other bacterial products is an important pathogenic factor. Activated Kupffer cells release proinflammatory cytokines, a process that is regulated by the CD14 endotoxin receptor (CD14). Recently, a C-->T (-159) polymorphism in the promoter region of the CD14 gene was detected and found to confer increased CD14 expression. In the present study, the association of CD14 promoter polymorphism with different forms of ALD was examined in 3 separate autopsy series. Among 442 men with valid alcohol-consumption data, 381 men had been moderate or heavy alcohol consumers. The allele frequency of the CD14 promoter genotype, determined by a modified cycle minisequencing technique, was 0.34 (CC), 0.51 (CT), and 0.16 (TT). The T allele was found to be associated with advanced ALD, i.e., with alcoholic hepatitis (odds ratio [OR]: 2.48; P = .018), and especially with cirrhosis (OR: 3.45; P = .004), but not with fatty liver, periportal fibrosis, or bridging fibrosis. The overall age-adjusted risk for cirrhosis was 3.08 (P = .01) for the carriers of the CT genotype, and 4.17 (P = .005) for the homozygous TT genotype. These results suggest that in the relatively isolated Finnish population, the T allele confers increased risk of alcoholic liver damage. In particular, TT homozygotes are at a high risk to develop cirrhosis.     

Genetic variation in the neuropeptide y gene promoter is associated with increased risk of tobacco smoking

Background: Neuropeptide Y (NPY) is a strong candidate gene regarding the pathophysiology of tobacco dependence. It has been associated with various addictive and psychiatric disorders, and closely interacts with the brain reward system. The aim of the present study was to test for association between a functional genetic variant in the NP-Y promoter gene (SNP rs16147) and tobacco smoking. Methods: In a population-based case-control multicenter study designed for tobacco addiction research, a total of 550 Caucasian current smokers, and 544 never-smokers were genotyped for SNP rs16147 and behaviorally characterized with the State-Trait Anxiety Inventory (STAI). Results: Subjects with TT genotype of the SNP rs16147 were significantly more frequently smokers than never-smokers (p = 0.046). In addition, TT genotype exhibited increased state anxiety scores compared to carriers of the C allele (p = 0.037). Conclusions: Our results provide evidence for an involvement of the functionally relevant SNP rs16147 in the pathophysiology of tobacco dependence. Further studies are needed to confirm our findings.     

CD14 gene polymorphism 159C/T in a group of patients with coronary artery disease from a population with high morbidity of cardiovascular diseases

BACKGROUND: A role of CD14 receptor in the inflammatory response is stimulation of monocytes and endothelial cells by lipopolysaccharide of Gram-negative bacteria. The reports about association of progression of atherosclerosis with CD14 gene polymorphism in different populations are conflicting. AIM: To assess if T to C exchange at position 159 of the CD14 gene correlates with age at the onset of first myocardial infarction (MI), severity of coronary atherosclerosis and number of risk factors in MI survivors in a local community characterised by high morbidity of cardiovascular diseases and whether this genotyping could be helpful in identifying patients with a high risk of MI at young age and beyond low number of risk factors. METHODS: Fifty-seven MI survivors (75.5% males) from 98 consecutive patients (pts) with coronary artery disease were included. The genotypes in position 159 of the CD14 gene were determined by polymerase chain reaction. The medical history concerning diabetes mellitus, arterial hypertension, dyslipidaemia, smoking and obesity was taken from every participant. Gensini score (GS) was calculated on the basis of coronarography. Age at first MI, value of GS and number of risk factors were analysed variables. The pts were divided into the decades of life, according to cumulated number of risk factors and into the terciles according to GS. Distribution of ages at first MI, pts with different number of risk factors and percent of pts belonging to determined terciles of GS were compared between subgroups with genotype CC and CT, TT. RESULTS: The CC genotype was detected in 25 (43.8%) pts, CT in 30 (52.6%) and TT in 2 (3.6%). Age at first MI ranged from 40 to 75 years, mean 58.7+/-7.23, values of GS ranged from 0 to 154, mean 48.6+/-25.7, and number of risk factors from 0 to 4, mean 1.92+/-0.99. No significant differences in distribution of ages at first MI, values of GS or number of risk factors were found between patients with CC and with CT or TT genotype in position 159 of CD14 receptor genotype. CONCLUSION: These data indicate that screening for CD14 159C/T polymorphism is unlikely to be a useful tool for risk assessment of MI at young age, independently of low number of risk factors, in a population with high morbidity from cardiovascular diseases.     

The -159C/T polymorphism in the promoter region of the CD14 gene is associated with advanced liver disease and higher serum levels of acute-phase proteins in heavy drinkers

BACKGROUND: Innate inflammatory responses to endotoxin (lipopolysaccharide) contribute to the development of alcoholic liver disease (ALD). A single-nucleotide polymorphism (-159C/T) in the promoter region of the gene coding for CD14 (a lipopolysaccharide receptor) could be associated with the development of ALD. We sought too investigate the relationship between the CD14/-159C/T polymorphism and advanced ALD and acute-phase protein levels in heavy drinkers. METHODS: A total of 138 heavy drinkers consecutively admitted to an Internal Medicine department were genotyped for the CD14/-159C/T polymorphism. Serum samples were analyzed for lipopolysaccharide-binding protein (LBP), soluble CD14 (sCD14), C-reactive protein (CRP), and immunoglobulin (Ig) A, IgG, and IgM. Patients with ascites or liver encephalopathy (n = 35) were classified as having advanced ALD. RESULTS: After adjusting for potential confounding variables, the CD14/-159TT genotype was positively associated with advanced ALD (odds ratio, 2.99; 95% confidence interval, 1.09-8.24, p = 0.03) and serum LBP (p = 0.01) and sCD14 (p = 0.04) levels. The CD14/-159C/T polymorphism was not associated with serum levels of CRP, IgA, IgG, or IgM. CONCLUSIONS: Our results support the notion that CD14/-159TT homozygous heavy drinkers have higher levels of the LPS-binding acute-phase proteins (LBP and sCD14) than do carriers of the CD14/-159C allele. Also, the CD14/-159TT genotype may be a risk factor for advanced ALD.     

Lack of association of the CD14/C-159T polymorphism with susceptibility and serological activity parameters of rheumatoid arthritis

OBJECTIVE: CD14, the monocyte receptor for lipopolysaccharides (LPS), is an important mediator of inflammatory processes. As the T-159C exchange in the promotor of the CD14 gene was reported to lead to enhanced CD14 expression, this could be a new susceptibility gene for rheumatoid arthritis (RA). We investigated whether this single nucleotide polymorphism (SNP) serves as a risk factor for disease development or has any influence on serological activity parameters of RA or soluble CD14 (sCD14) levels. PATIENTS AND METHODS: A total of 130 patients with RA, diagnosed according to the revised American College of Rheumatology (ACR) criteria, and 130 healthy subjects, all Caucasians, were genotyped using polymerase chain reaction (PCR). Genotype frequencies were compared by chi2 analysis. RESULTS: Forty (31%) patients vs. 39 (30%) controls were genotyped CC; 71 (55%) vs. 67 (52%) were heterozygous, and 19 (15%) vs. 24 (19%) showed the TT genotype (p = 0.7). Accordingly, the allele frequency was equally distributed (p = 0.8). There was also no significant difference in genotype distribution between subgroups of patients categorized according to serological activity parameters and sCD14 levels. CONCLUSION: We found no association between the CD14/C-159T polymorphism and increased risk for the development of RA or serological disease activity parameters or sCD14 levels.     

CD14 expression on monocytes and soluble CD14 plasma levels in correlation to the promotor polymorphism of the endotoxin receptor CD14 gene in patients with inactive Crohn's disease

BACKGROUND/AIMS: The association of the single nucleotide polymorphism in the promotor of the lipopolysaccharide receptor CD14 gene (T/C at position -159) with Crohn's disease has recently been demonstrated. This CD14 polymorphism is a potential predisposition factor responsible for inter-individual differing inflammatory reactions involving the CD14 receptor. We studied the correlation between the CD14 genotype (CC, CT, TT) and the membrane-bound CD14 monocyte expression and soluble CD14 in patients with inactive Crohn's disease. METHODOLOGY: In 23 patients and 29 healthy volunteers the membrane-bound CD14 density on unstimulated monocytes and soluble CD14 plasma levels were examined using quantitative flow cytometry and enzyme-linked immunosorbent assay. RESULTS: In normal controls membrane-bound CD14 monocyte density did not differ significantly between the genotypes CC, CT, or TT. In contrast, patients with inactive Crohn's disease and genotype TT showed a significantly lower membrane-bound CD14 density on monocytes compared to patients with genotype CC. Soluble CD14 plasma levels were significantly higher in patients with inactive Crohn's disease compared to the same genotype of healthy controls, but there was no significant difference between the genotypes CC, CT, and TT. CONCLUSIONS: Our data show that the membrane-bound CD14 monocyte expression and the soluble CD14 plasma levels in patients with inactive Crohn's disease completely differ from that in healthy individuals. In order to develop individualized therapy strategies further studies should be carried out to evaluate whether the TT genotype is associated with differences in the clinical course of Crohn's disease and in the response to antibacterial treatment.     

Association between a sequence variant in the IL-4 gene promoter and FEV(1) in asthma.

Recent family-based studies have revealed evidence for linkage of human chromosome 5q31 to the diagnosis of asthma, elevated serum IgE levels, and bronchial hyperresponsiveness. Among the candidate genes in this region is the gene encoding for human interleukin-4 (IL-4). We reasoned that this gene could also serve as a candidate gene with respect to asthma severity as indicated by the FEV(1) measured when bronchodilator treatment was withheld. To test this hypothesis, we examined a large population of patients with asthma (ascertained without respect to genetic characteristics), for associations between a genetic variant in the IL-4 promoter region (C-589T) and asthma severity, as indicated by FEV(1). We used amplification by the polymerase chain reaction followed by BsmF1 restriction digestion to assign genotypes at the IL-4 promoter C-589T locus. We compared genotypes at this locus in 772 Caucasian and African American patients with asthma of varying severity, and we used multiple regression analysis to relate genotypic findings to FEV(1). Among white individuals, the homozygous presence of the C-589T IL-4 promoter genotype (TT) was associated with a FEV(1) below 50% of predicted (p = 0.013; OR, 1.44; 95% CI: 1.09 to 1.90). Subjects with the TT genotype had mean FEV(1) (% predicted) values 4.5% lower than those of subjects with the wild-type (CC) genotype at this locus. FEV(1) values of white patients with a CC or CT genotype were broadly distributed, whereas the TT genotype was associated with a narrow distribution of low FEV(1) values. The frequency of the T allele was significantly greater (p = 1 x 10(-)(23)) among African American asthmatics (0.544) than among white asthmatics (0.183). These data provide the first evidence associating FEV(1) in patients with asthma and genetic determinants at any locus. Our data are consistent with the idea that the FEV(1) in asthma is the result of multiple factors; one of these factors is the genotype at the IL-4 C-589T locus. This locus is associated with a small but significant decrement in pulmonary function among white asthmatic subjects.     

白细胞介素13基因启动子-1055位点基因型与慢性阻塞性肺疾病的相关性研究

目的 研究慢性阻塞性肺疾病(COPD)患中白细胞介素13(IL-13)基因启动子-1055位点基因型分布频率，初步探讨此位点突变在COPD发病中的作用。方法 选取111例COPD患作为病例组，97例无气流阻塞的其他患作为对照组，高盐沉淀法从静脉血中提取基因组DNA，应用等位基因特异性聚合酶链反应(PCR)法，检测IL-13基因启动子-1055位点的多态性，通过对PCR产物测序，验证等位基因特异性PCR方法的特异性。应用SPSS软件进行统计学分析，LDgistic回归排除混杂因素的干扰，分析此位点基因多态与COPD的相关性，分层分析此基因多态与吸烟的相互作用。结果 COPD组和对照组中TT基因型的频率分别是11．7％(13／111)和13．4％(13／97)，P=0．713，应用Logistic回归排除年龄、性别、吸烟和合并其他疾病的影响后，P=0．244；采用分层分析方法对IL-13-1055位点TT基因型与吸烟因素进行综合分析，同时应用Logistic回归排除混杂因素的干扰，结果表明不吸烟样本中IL-13-1055位点TT基因型的OR值为0．40(95％CI：0．09～1．77)，吸烟样本中增加到6．40(95％CI：1．62～25．39)。COPD患TT基因型与各临床表型之间关系的研究显示，TT基因型与COPD家族史显正相关，OR值为7．67(95％CI：1．37～43．80)。结论 在中国北京汉族人群中，IL-13-1055位点TT基因型吸烟发生COPD的危险性可能高于CC／CT基因型吸烟。在有家族史的人群中，IL-13-1055位点TT基因型可能更易发生COPD。     

CD14 tobacco gene-environment interaction modifies asthma severity and immunoglobulin E levels in Latinos with asthma

BACKGROUND: A recent family-based genomewide screen revealed linkage between the 5q31 region and the diagnosis of asthma, but only in those exposed to environmental tobacco smoke (ETS). Among the candidate genes in this region is CD14. METHODS: To determine whether polymorphisms in the CD14 gene are related to this gene-by-environment interaction in Latinos, we used both family-based and cross-sectional cohort analysis to test for interactions between CD14 genotypes/haplotypes, exposure to ETS, and asthma-related phenotypes in 659 Mexican and Puerto Rican families. RESULTS: We identified 21 single nucleotide polymorphisms (SNPs) in the CD14 gene by sequencing 72 Puerto Ricans, Mexicans, and African Americans with asthma. Three SNPs, -810, -159, and +1437, were further genotyped in families with asthma. Among all subjects with asthma exposed to ETS, without regard to ethnicity, CD14 +1437 genotypes were associated with asthma severity. SNP +1437 GG or GC genotypes were significantly associated with lower baseline FEV1 using both family-based (p = 0.0009) and cross-sectional cohort (p = 0.03) analyses. Subjects with asthma with the GG or GC genotypes who were exposed to ETS had mean baseline FEV1 (% predicted) values 8.6% lower than subjects not exposed to ETS (p = 0.03). As previously observed in whites, we found an interaction between plasma IgE levels, SNP -159 genotypes, and ETS exposure (p = 0.0002). The lowest IgE levels were in those subjects with the TT genotype and who were exposed to ETS regardless of ethnicity. CONCLUSIONS: Our data suggest a gene-by-environment interaction between CD14 genotypes and ETS, which affects pulmonary function and IgE levels among Latinos with asthma.     

Ulcerative colitis is associated with a promoter polymorphism of lipopolysaccharide receptor gene,CD14

BACKGROUND: Inflammatory bowel disease (IBD) is a multifactorial disease with a significant genetic background. Evidence is accumulating that molecules such as CD14, which interact with luminal bacterial constituents, are involved in the pathogenesis. It has recently been shown that the T allele of the 5'-flanking region of the CD14 gene at position -159 is related to high expression of CD14. In further exploring the genetic background of IBD, we investigated this novel polymorphism of CD14 gene in patients with ulcerative colitis or Crohn disease. METHODS: DNA was obtained from 101 patients with ulcerative colitis, 82 with Crohn disease and 123 healthy controls. All were typed for the promoter polymorphism of the CD14 gene at position -159 by restriction fragment length polymorphism analysis. Serum samples were obtained from 105 healthy controls and serum sCD14 levels were measured. RESULTS: T allele frequencies were 57.4%, 48.2% and 44.7% in ulcerative colitis, Crohn disease and healthy controls, respectively. The T allele and T/T genotype frequencies were significantly higher in ulcerative colitis patients than in healthy controls (P = 0.0074, OR = 1.67, 95% CI = 1.15-2.42, P = 0.022, OR= 1.96 95% CI: 1.10-3.48, respectively). The sCD14 level was significantly higher in TT genotype populations than CC (P = 0.0205). CONCLUSIONS: The promoter polymorphism of the CD14 gene at -159T plays a significant role in regulating the CD14 expression and is positively associated with ulcerative colitis, and this polymorphism may confer a genetic predisposition to ulcerative colitis. The results also support the concept that bacterial constituents may be involved in the pathogenesis of ulcerative colitis.     

Angiotensin-converting-enzyme gene polymorphisms, smoking and chronic obstructive pulmonary disease

While tobacco smoking is the main risk factor for chronic obstructive pulmonary disease (COPD) only a fraction of smokers go on to develop the disease. We investigated the relationship between the insertion (I) – deletion (D) polymorphisms in the Angiotensin converting enzyme (ACE) gene and the risk of developing COPD in smokers by determining the distribution of the ACE genotypes (DD, ID and II) in 151 life-long male smokers. 74 of the smokers had developed COPD (62 ± 2 years; FEV₁ 44 ± 6 % reference) whereas the rest retained normal lung function (56 ± 2 yrs; FEV₁ 95 ± 3 % reference). In addition, we genotyped 159 males recruited randomly from the general population. The prevalence of the DD genotype was highest (p = 0.01) in the smokers that developed COPD and its presence was associated with a 2-fold increase in the risk for COPD (OR 2.2; IC95% 1.1 to 5.5). Surprisingly, the 151 individuals in the smoking population did not demonstrate Hardy-Weinberg equilibrium unlike the 159 recruited from the general population. Our results suggest that ACE polymorphisms are associated with both the smoking history of an individual and their risk of developing COPD.     

Age-specific relationship between CD14 and atopy in a cohort assessed from age 8 to 25 years

CD14 influences postnatal switching of T helper cell responses. CD14 C-159T has been associated with altered CD14 and IgE levels in cross-sectional studies. Identifying whether associations vary with age requires data from children of the same age followed longitudinally over many years. In this study, an unselected population with extensive longitudinal data was used to test the hypothesis that CD14 C-159T was associated with early-onset atopy. A total of 305 subjects were assessed on up to seven occasions between ages 8 and 25 years by questionnaire, histamine challenge, and skin prick test. For atopy, airway hyperresponsiveness (AHR), and wheeze, each subject was classified as having early onset, late onset, or no disease onset during follow-up. Compared with subjects with -159CT and -159TT, subjects with -159CC had an odds ratio of 2.2 (p = 0.018) for early-onset atopy and an odds ratio of 2.6 (p = 0.019) for early-onset AHR. Cross-sectional analysis showed increased prevalence of -159CC in subjects with atopy and AHR in childhood but not adulthood. These data suggest that the influence of CD14 -159C on the atopic phenotype may be age specific, exerting an effect during midchildhood, which is no longer apparent by early adulthood.     

Genetic polymorphism in CD14 gene,a co-receptor of TLR4 associated with non-alcoholic fatty liver disease

AIM To evaluate the pathogenic role of toll-like receptor(TLR) gene polymorphisms in patients with nonalcoholic fatty liver disease(NAFLD).METHODS Two hundred and fifty subjects(NAFLD = 200, healthy volunteers = 50) underwent polymerase chain reaction and restriction fragment length polymorphism to assess one polymorphism in the toll-like receptor 2(TLR2) gene(A753G), two polymorphisms in the TLR4 gene(TLR4 Asp299 Gly and Thr399 Ile allele), and two polymorphisms in the cluster of differentiation 14(CD14)(C-159 T and C-550T) gene, a co-receptor of TLR4. Association of TLR gene polymorphisms with NAFLD and its severity was evaluated by genetic models of association.RESULTS On both multiplicative and recessive models of gene polymorphism association, there was significant association of CD14 C(-159) T polymorphism with NAFLD; patients with TT genotype had a 2.6 fold increased risk of developing NAFLD in comparison to CC genotype. There was no association of TLR2 Arg753 Gln, TLR4 Asp299 Gly, Thr399 Ile, and CD14 C(-550) T polymorphisms with NAFLD. None of the TLR gene polymorphisms had an association with histological severity of NAFLD.CONCLUSION Patients with CD14 C(-159) T gene polymorphism, a co-receptor of TLR4, have an increased risk of NAFLD development.     

CD14启动子-260位点基因多态性对糖尿病肾病的影响

目的探讨CD14启动子-260位点基因多态性对糖尿病肾病（DN）的影响。方法应用PCR直接测序法对437例2型糖尿病（T2DM）患者（T2DM组）及145例正常者（对照组）的CD14启动子C-260T基因多态性进行分析。结果两组CD14启动子-260位点基因型分布及等位基因频率均无统计学差异（P〉0．05）;非DN与DN患者比较,其CD14启动子-260位点CC基因与CT＋TT基因有统计学差异（P〈0．05）。结论CD14启动子-260C／T基因多态性与糖尿病发病无相关性,但其CC基因是T2DM患者进展为DN的遗传学风险因素。     

Association of promoter polymorphism of the CD14 C （-159） T endotoxin receptor gene with chronic hepatitis B

INTRODUCTION An estimated 350 million persons worldwide are infected with hepatitis B virus (HBV). Hepatitis B carriers are at risk for development of cirrhosis and hepatocellular carcinoma. Persons with chronic hepatitis B infection need life-long monito…