The CD14-260 C --> T promoter polymorphism co-segregates with the tumor necrosis factor-alpha (TNF-alpha)-308 G --> A polymorphism and is associated with the interleukin-1 beta (IL-1 beta) synthesis capacity of human leukocytes

Genetic variations contribute to the interindividual variance in the cytokine response to endotoxin. The gene of tumor necrosis factor-alpha (TNF-alpha) carries a polymorphism at position -308 of the promoter, consisting of a G/A exchange. To further elucidate the inherited mechanisms influencing cytokine levels, healthy human blood donors were studied. Genotyping for the TNF-alpha -308 and the CD14 -260 C/T promoter polymorphisms was carried out by real-time polymerase chain reaction assay using specific fluorescence-labelled hybridisation probes. A human whole blood assay was used to study the leukocyte TNF-alpha and IL-1 beta synthesis capacity upon endotoxin stimulation. We found a linkage disequilibrium between the TNF-alpha -308 G/A and the CD14 -260 C/T polymorphisms (p = 0.043). The CD14 -260 polymorphism was associated with IL-1 beta levels (p = 0.033) and higher values were found in C homozygotes. No association was found between the CD14 -260 genotypes or the TNF-alpha -308 - CD14 -260 genotypes and the TNF-alpha response.     

The association between CD14 gene C-260T polymorphism and coronary heart disease risk: a meta-analysis

Monocyte differentiation antigen CD14 is considered an important cell-activating mediator of inflammatory responses that may result in atherosclerosis, coronary heart disease (CHD), thrombus formation, and myocardial infarction (MI). A common C-260T polymorphism in the promoter of the CD14 gene, the trans-membrane receptor of lipopolysaccharides, has been inconsistently associated with CHD. To investigate this inconsistency, we performed a meta-analysis of 28 studies involving a total of 13,335 CHD cases and 7,979 controls for C-260T of the CD14 gene to evaluate the effect of CD14 on genetic susceptibility for CHD. An overall random effects odds ratio of 1.24 (95 % CI: 1.12–1.36, P < 10^?5) was found for T allele. Significant results were also observed using dominant (OR = 1.34, 95 % CI: 1.17–1.54, P < 10^?4) or recessive genetic model (OR = 1.25, 95 % CI: 1.10–1.41, P = 0.0004). There was strong evidence of heterogeneity (P < 10^?5), which largely disappeared after stratification by ethnicity. After stratified by ethnicity, significant results were found in East Asians; whereas no significant associations were found among Caucasians and other ethnic populations in all genetic models. In the stratified analysis according to sample size, CHD endpoints, and HWE status, significantly increased risks for the polymorphism were found in all genetic models. In conclusion, our results indicate that the CD14 C-260T polymorphism is a risk factor of CHD, especially in East Asians. However, additional very large-scale studies are warranted to confirm our results.     

Polymorphisms of CARD15/NOD2 and CD14 genes in New Zealand Crohn's disease patients

Polymorphisms in the CARD15/NOD2 gene, which encodes a cytosolic protein involved in bacterial recognition, are associated with development of Crohn's disease (CD). Other potential susceptibility genes such as CD14 may compound the risk of developing CD. We examined the frequency of the three major CARD15 risk alleles (3020insC/L1007fsinsC, G908R and R702W), and a functional polymorphism (-159C/T) in the promoter of the CD14 gene in 185 CD patients in New Zealand and 187 ethnically matched controls. The frequencies of the 3020insC (8.1 vs 0.8%, P < 0.0001), G908R (3.5 vs 2.4%, P = 0.37) and R702W (7.3 vs 5.1%, P = 0.21) alleles in CD patients and controls, respectively, were similar to those described in Australia, and the ancestral countries of Scotland, Ireland and the UK. Only the 3020insC polymorphism was found to be a significant risk factor for CD in our New Zealand cohort (odds ratio = 10.91 [95% confidence intervals 3.30-36.08]; P < 0.0001 for heterozygotes), but not a single patient was homozygous for the 3020insC polymorphism. The T allele (51 vs 50%, P = 0.77) and TT genotype (26 vs 24%, P = 0.84) frequencies of the -159C/T CD14 gene promoter polymorphism did not significantly differ between CD patients and controls. In summary, our findings provide evidence that the CARD15 3020insC risk allele influences disease susceptibility in a small proportion (<17%) of New Zealand CD patients, whereas there was no evidence that the CD14 -159C/T polymorphism is associated with CD.     

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 theCD14 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 ofCD14 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 theCD14 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.     

Lipoprotein(a) and its position among other risk factors of atherosclerosis

Lipoprotein(a) [Lp(a)] comprises of an LDL particle and apolipoprotein(a) [apo(a)] and its elevated levels are considered a risk factor for atherosclerosis. The aim of our study was to find out whether elevated Lp(a) levels are associated with increased risk of atherosclerosis in patients with multiple other risk factors. We further tested the association of three polymorphisms of the apo(a) gene promoter with Lp(a) levels. No significant correlation was detected between Lp(a) levels and lipid and clinical parameters tested. The study demonstrated a significantly (p=0.0219) elevated Lp(a) level (mean 28+/-35 mg/dl, median 0.14) in patients with coronary heart disease (CHD). In a group with premature CHD the correlation was not significant anymore. There was a significant correlation between polymorphic loci of the promoter region of apo(a) gene and Lp(a) levels (+93C T, p=0.0166, STR, p<0.0001). Our study suggests that elevated Lp(a) level is an independent risk factor of CHD in carriers of other important CHD risk factors. Observed association of sequence variants of the promoter of apo(a) gene with Lp(a) levels is caused in part due to linkage to a restricted range of apo(a) gene length isoforms.     

Genetic variations in CD14 promoter and acute lymphoblastic leukemia susceptibility in a Chinese population

Recent findings suggest that CD14 may play a role in tumor development. Previous case-control studies have revealed that CD14 -260C/T and -651?C/T polymorphisms contribute to the risk of human diseases. However, the relationship between these two functional polymorphisms and susceptibility to acute lymphoblastic leukemia (ALL) has not been explored. In this study, we performed a case-control study in a Chinese population. We found that an increased risk of ALL was associated with the -260?TT (odds ratio [OR]=1.85, 95% confidence interval [CI]=1.26-2.63) genotype compared with the CT or CC genotype. No significant association was found between -651?CC genotype and ALL (OR=1.13, 95% CI=0.77-1.69). Moreover, the increased risk was only associated with the -260?TT genotype in B-ALL (OR=1.99, 95% CI=1.34-3.01) but not in T-ALL (OR=1.48, 95% CI=0.79-2.84). The findings suggest that CD14-260C/T polymorphism can contribute to B-ALL risk in a Chinese population.     

Polymorphisms in the CNTF and CNTF receptor genes are associated with muscle strength in men and women.

Genotypic associations between polymorphisms in the ciliary neurotrophic factor (CNTF) and CNTF receptor (CNTFR) genes and muscular strength phenotypes in 154 middle-aged men (45-49 yr) and 138 women (38-44 yr) and 99 older men (60-78 yr) and 102 older women (60-80 yr) were tested to validate earlier association studies. Allelic interaction effects were hypothesized between alleles of CNTF and CNTFR. We performed analysis of covariance with age, height, and fat-free mass (FFM) as covariates. FFM was anthropometrically estimated by the equation of Durnin-Womersley. Isometric, concentric, and eccentric torques for the knee flexors (KF) and extensors (KE) were measured using Biodex dynamometry. In the older male group, T-allele carriers of the C-1703T polymorphism in CNTFR performed significantly better on all noncorrected KF torques, whereas only noncorrected KE isometric torque at 120 degrees and concentric torque at 240 degrees/s were higher than the C/C homozygotes (P < 0.05). When age, height, and FFM were used as covariates, T-allele carriers performed only better on KE and KF isometric torque at 120 degrees (P < 0.05). Concentric KF torque at 180 degrees/s was lower in middle-aged female A-allele carriers compared with the T/T subjects for the T1069A polymorphism in CNTFR. After correction for age, height, and FFM, middle-aged female A-allele carriers exhibited lower values on all concentric KF strength measures and isometric torque at 120 degrees . There was a lack of association with the CNTF G-6A polymorphism in men, with inconclusive results for a limited number of phenotypes in women. No significant CNTF/CNTFR allele interaction effects were found. Results indicate that CNTFR C-1703T and T1069A polymorphisms are significantly associated with muscle strength in humans.     

The MMP-9 -1562 C/T Polymorphism in the Presence of Metabolic Syndrome Increases the Risk of Clinical Events in Patients with Coronary Artery Disease

Background and Objectives

Elevated levels of matrix metalloproteinase (MMP)-9 have been associated with the metabolic syndrome (MetS) and cardiovascular events. The MMP-9 −1562 C/T polymorphism has furthermore been shown as a risk factor for coronary artery disease (CAD). The non-favourable cardiometabolic state in MetS may increase the risk. We aimed to investigate the influence of MMP-9 −1562 C/T polymorphism in subjects with CAD and MetS.

Methods

Patients (n = 1000) with verified CAD stratified in Mets +/− (n = 244/756), were analyzed for the MMP-9 −1562 C/T polymorphism and related to clinical events after 2 years follow-up. Serum levels of total MMP-9 and tissue inhibitor of matrix metalloproteinases (TIMP)-1were analyzed in all, whereas MMP-9 activity, extracellular matrix metalloproteinase inducer (EMMPRIN), and expression of the two genes were analyzed in a subset of 240 randomly selected patients.

Results

Totally, 106 clinical endpoints were recorded. In MetS; the T-allele associated with 5.5 fold increase in event rate (p<0.0001), increased with number of MetS components, a 117% increase in total MMP-9 levels (TT homozygous, p = 0.05), significantly higher total- and endogenous active MMP-9 and TIMP-1 levels (p<0.01 all), and EMMPRIN was inversely correlated with pro- and endogenous active MMP-9 (p<0.05, both). In non-MetS; the T-allele was not associated with new events, nor higher MMP-9 levels. EMMPRIN was significantly correlated with total MMP-9 and TIMP-1 (p<0.01, both) and the two genes were inter-correlated (p<0.001).

Conclusion

In CAD patients with MetS, the MMP-9 T-allele increased the risk of clinical events, probably mediated through elevated MMP-9 levels and altered MMP-9 regulation.     

Association of GNB3 C825T polymorphism with plasma electrolyte balance and susceptibility to hypertension

The role of G-protein activation in cardiovascular disorders is well-known. G-protein β3 subunit (GNB3) C825T polymorphism is associated with increased intracellular signal transduction. We investigated the role of the variant in plasma sodium and potassium concentrations and association with hypertension. 345 healthy controls and 455 patients with essential hypertension were enrolled. Plasma renin activity and aldosterone concentration were measured. The variant, typed by SNaPshot, was analyzed on an ABI Prism 3100 Genetic Analyzer and GeneScan. The TT genotype and T allele were over-represented in the patients (p < 0.001, p < 0.0001). Multiple-logistic regression disclosed that the risk of hypertension was significantly greater for TT (p < 0.0001, OR = 6.1, CI = 2.9-12.7). One-way ANOVA revealed that hypertensive T-allele carriers (CT+TT), compared to non-carriers (CC), had a greater body mass index (BMI), mean arterial pressure (MAP) and PAC (p = 0.01, p = 0.01, p < 0.0001, respectively); while the patients with 825TT risk genotype showed higher plasma sodium and lower potassium (p < 0.0001, each). The results strongly emphasize, not only the role of C825T polymorphism by the induction of increased G-protein activity and enhancement of Na/h exchangers, but also the association with higher plasma sodium and lower potassium levels, high BMI and susceptibility to hypertension.     

Interleukin 6 polymorphism corresponds to the number of severely stenosed coronary arteries

IL6 gene promoter polymorphisms may influence the outcome of cardiovascular diseases. The aim of our study was to find out whether the -174G>C polymorphism, as well as the IL6 secretory profile, may be linked to the number of severely (> or = 75%) occluded coronary arteries in patients with advanced coronary heart disease (CHD). Three hundred and twenty patients awaiting elective coronary artery bypass grafting were enrolled into the study. Blood was taken the day before surgery. The PCR-RFLP method was used for IL6 gene polymorphism analysis. Spontaneous IL6 release was measured by bioassay in supernatants of whole blood cell cultures (WBCC) incubated for 24 h and 48 h. We found that significantly more patients with triple vessel disease were found within the -174GG group as compared to the -174GC and CC genotype carriers. The highest IL6 serum levels were found in the -174GG and the lowest in the -174CC genotype patients. Spontaneous in vitro IL6 secretion appeared to be significantly higher at all time points in the -174GG as compared to the CC and GC genotype carriers. The serum concentration of IL6 and the spontaneous IL6 secretion were directly related to the number of obstructed coronary vessels. Our results emphasize the role of IL6 as an important, non-classical risk factor predicting the number of severely affected coronary vessels.     

Association between the −159C/T CD14 gene polymorphism and tuberculosis in a Korean population

The aim of the present study was to confirm the association between the CD14 −159C/T polymorphism and tuberculosis in the Korean population and to elucidate the functional basis for this putative association. CD14 −159C/T genotypes were determined by PCR – restriction fragment length polymorphism analysis in 274 tuberculosis patients and 422 healthy controls. Recombinant CD14 promoter–luciferase reporter constructs, including the −159T or −159C allele, were transfected into K562 and BEAS-2B cells, and luciferase activities were measured and compared. Levels of serum sCD14 and interferon-γ secreted by peripheral blood mononuclear cells (PBMCs) were measured using enzyme-linked immunosorbent assay.The frequency of −159TT genotypes was higher in tuberculosis patients than in healthy controls. The promoter activity of the −159T allele was higher than that of the −159C allele. Serum sCD14 levels were higher among tuberculosis patients with −159TT genotypes than among those with −159CC genotypes and interferon-γ release by PBMCs was decreased in subjects with −159TT genotypes. In conclusion, the −159TT CD14 genotypes were associated with tuberculosis development in Koreans. This association might be a result of the higher promoter activity of the −159T allele, the higher level of sCD14, and the decreased interferon-γ secretion in subjects with −159TT genotypes.     

Hepatic lipase: a marker for cardiovascular disease risk and response to therapy

PURPOSE OF REVIEW: Hepatic lipase plays a key role in the metabolism of pro-atherogenic and anti-atherogenic lipoproteins affecting their plasma level as well as their physico-chemical properties. However, controversial evidence exists concerning whether hepatic lipase is pro or anti-atherogenic. The goal of this review is to summarize recent evidence that connects the enzyme to cardiovascular disease. The potential impact of genetic determinants of hepatic lipase activity in modulating both the development of coronary and carotid atherosclerosis will be discussed based on hepatic lipase proposed roles in lipoprotein metabolism. RECENT FINDINGS: Twenty to 30% of individual variation of hepatic lipase activity is accounted for by the presence of a common polymorphism in the promoter region (-514 C to T) of the hepatic lipase gene (LIPC). This polymorphism, via its impact on hepatic lipase synthesis and activity, appears to contribute to (1) individual susceptibility to cardiovascular disease: the presence of the T allele (low hepatic lipase activity) may carry a marginally increased risk of atherosclerosis; (2) carotid plaque composition and individual susceptibility to cerebrovascular events: the presence of the C allele (high hepatic lipase activity) is associated with increased carotid intima-media thickness and abundance of macrophages in the carotid plaque (unstable plaque); and (3) response of cardiovascular disease patients to lipid-lowering therapy: patients with the CC genotype have the greatest clinical benefit from intensive lipid-lowering therapy. SUMMARY: Convincing evidence shows that hepatic lipase plays a key role in remnant lipoprotein catabolism as well as in remodeling of LDL and HDL particles. The anti or pro-atherogenic role of hepatic lipase is likely to be modulated by the concurrent presence of other lipid abnormalities (i.e. increased LDL cholesterol levels) as well as by the genetic regulation of other enzymes involved in lipoprotein metabolism. Characterization of patients by their LIPC genotype will contribute to a better definition of individual risk of coronary and cerebrovascular events, specifically in patients with qualitative (small, atherogenic LDL and low HDL2 cholesterol) rather than quantitative lipid abnormalities for whom the routine lipid profile may underestimate the risk of coronary and cerebrovascular disease.     

Functional gene polymorphisms in the serotonin system and traumatic life events modulate the neural basis of fear acquisition and extinction

Fear acquisition and extinction are crucial mechanisms in the etiology and maintenance of anxiety disorders. Moreover, they might play a pivotal role in conveying the influence of genetic and environmental factors on the development of a (more or less) stronger proneness for, or resilience against psychopathology. There are only few insights in the neurobiology of genetically and environmentally based individual differences in fear learning and extinction. In this functional magnetic resonance imaging study, 74 healthy subjects were investigated. These were invited according to 5-HTTLPR/rs25531 (S+ vs. L(A)L(A); triallelic classification) and TPH2 (G(-703)T) (T+ vs. T-) genotype. The aim was to investigate the influence of genetic factors and traumatic life events on skin conductance responses (SCRs) and neural responses (amygdala, insula, dorsal anterior cingulate cortex (dACC) and ventromedial prefrontal cortex (vmPFC)) during acquisition and extinction learning in a differential fear conditioning paradigm. Fear acquisition was characterized by stronger late conditioned and unconditioned responses in the right insula in 5-HTTLPR S-allele carriers. During extinction traumatic life events were associated with reduced amygdala activation in S-allele carriers vs. non-carriers. Beyond that, T-allele carriers of the TPH2 (G(-703)T) polymorphism with a higher number of traumatic life events showed enhanced responsiveness in the amygdala during acquisition and in the vmPFC during extinction learning compared with non-carriers. Finally, a combined effect of the two polymorphisms with higher responses in S- and T-allele carriers was found in the dACC during extinction. The results indicate an increased expression of conditioned, but also unconditioned fear responses in the insula in 5-HTTLPR S-allele carriers. A combined effect of the two polymorphisms on dACC activation during extinction might be associated with prolonged fear expression. Gene-by-environment interactions in amygdala and vmPFC activation may reflect a neural endophenotype translating genetic and adverse environmental influences into vulnerability for or resilience against developing affective psychopathology.     

Functional polymorphism located in MMP-9 gene promoter is strongly associated with obesity

The adipose tissue expansion is accompanied by remodeling of extracellular matrix performed by matrix metalloproteinases (MMPs). Higher plasma and tissue MMP-9 levels are found in obese; therefore, we evaluated if the functional C(-1562)T polymorphism (rs3918242) located in promoter region of the MMP-9 gene is associated with obesity in women. We studied 112 lean and 114 obese women. Plasma MMP-9 and tissue inhibitor of MMP-9 (TIMP)-1 were measured using enzyme-linked immunosorbent assay. We found different genotype frequencies between lean and obese women (p=0.008), prevailing T-allele in obese (2.3-fold). However, although obese women present higher levels of plasma MMP-9, lack of modulation by the polymorphism was found (all p>0.05). Our findings suggest that C(-1562)T polymorphism may contribute to pathogenetic mechanisms involved in the development of obesity in women.     

Effects of the PPARG P12A and C161T gene variants on serum lipids in coronary heart disease patients with and without Type 2 diabetes

We investigated whether PPAR-γ2 gene polymorphisms are associated with serum lipids and the occurrence of coronary heart disease (CHD) prospectively characterised for the presence or absence of Type 2 diabetes in a Turkish population. Our study included 202 patients with CHD (102 with diabetes, 100 without diabetes) and 105 controls. PPARγ genotypes were determined by PCR-RFLP technique. The PPARγ-C161T CC homozygote genotype was associated with significantly increased CHD risk when compared with the T allele carriers (CT+TT) in CHD patients with diabetes (OR:1.951, 95%CI: 1.115-3.415, P = 0.019), whereas PPARγ-P12A polymorphism was not associated with CHD risk (P > 0.05). Serum HDL-C levels were significantly lower in controls with the P12A heterozygote when compared with the P12P homozygote (P = 0.002). In the CHD patients with diabetes, CT heterozygote genotype showed higher serum triglyceride than the CC homozygote genotype (CT:2.42 ± 1.89 vs. CC:1.61 ± 0.21, P = 0.015). Our findings shows the association of these two polymorphisms with serum triglyceride levels, which was increased in the order of P12P-CC < P12P-CT < P12A-CC < P12A-CT in the CHD patients with diabetes. Furthermore, we observed that the increasing effects of the CT genotype on serum triglyceride levels could be modified by PPARγ P12A polymorphism (P12A-CT:2.30 ± 1.75 vs. P12P-CC:1.79 ± 1.14, P = 0.028). We suggested that homozygote CC genotype of the PPARγ C161T polymorphism might be associated with an increased CHD risk especially in patients with diabetes. We observed that the C161T CT heterozygote genotype shows an unfavorable effect on serum lipid profile in CHD patients with diabetes and this effect was weaken with the presence of P12P homozygote genotype.     

Association of Hepatic Lipase -514T Allele with Coronary Artery Disease and Ankle-Brachial Index,Dependence on the Lipoprotein Phenotype: The GENES Study

Objectives

Relationship between hepatic lipase (LIPC) polymorphism and coronary artery disease (CAD) has often led to contradictory results. We studied this relation by genotyping rs1800588 in the LIPC promoter in a case-control study on CAD (the GENES study). We also investigated the relationship between this polymorphism and the ankle-brachial index (ABI), which is predictive of atherosclerosis progression and complications in patients at high cardiovascular risk.

Methods

557 men aged 45–74 with stable coronary artery disease and 560 paired controls were genotyped for rs1800588. Medical data, clinical examination including determination of ABI and biological measurements related to cardiovascular risk factors enabled multivariate analyses and multiple adjustments.

Results

CAD cases showed a higher T-allele frequency than controls (0.246 vs 0.192, p = 0.003). An interaction has been found between LIPC polymorphism and triglycerides (TG) levels regarding risk of CAD: TT-homozigosity was associated with an Odds ratio (OR) of 6.4 (CI: 1.8–22.3) when TG were below 1.5 g/L, but no association was found at higher TG levels (OR = 1.34, CI: 0.3–5.9). The distribution of LIPC genotypes was compared between CAD patients with normal or abnormal ABI and impact of LIPC polymorphism on ABI was determined. Following multiple adjustments, association of the T-allele with pejorative ABI (<0.90) was significant for heterozygotes and for all T-carriers (OR = 1.55, CI: 1.07–2.25).

Conclusion

The -514T LIPC allele is associated with CAD under normotriglyceridemic conditions and constitutes an independent determinant of pejorative ABI in coronary patients.     

Effect of G(-174)C polymorphism in interleukin-6 gene on cardiovascular disease in type 2 diabetes patients

Interleukin-6 (IL-6) is an important pro-inflammatory cytokine of relevance to cardiovascular diseases. The aim of this case-control study was to evaluate the association between the G(-174)C functional polymorphism in the IL-6 gene and risk of cardiovascular disease (CVD) in type 2 diabetes patients. We examined 1090 patients with T2DM and 612 controls. All subjects were genotyped for the G(-174)C polymorphism by polymerase chain reaction (PCR) and restriction analysis. There were no significant differences in the distribution of genotypes and alleles between T2DM patients and healthy controls. Significantly higher C allele frequency was observed in CVD+ patients compared to CVD- subgroup (53% vs. 32%, p < 0.0001). The odds ratio for C allele was 2.4 (95% CI 1.99–2.9, p < 0.0001) and for CC genotype 4.55 (95% CI 3.12–6.63, p < 0.000). When the distribution of G(-174)C polymorphism was compared in subgroups with different clinical phenotypes of CVD, a significant association of CC genotype with myocardial infarction was observed. Forty eight percent of patients with MI had the CC genotype compared to 22% of patients without MI (p < 0.0001). In conclusion, type 2 diabetes patients carrying the C allele of the IL-6 G(-174)C polymorphism have a significantly increased risk of CVD.     

CD14-159 and -260 gene polymorphisms are associated with HBV-related cirrhotic injury in Chinese Han patients

The present study aimed to investigate the association between TLR4 mutations (Asp299Gly and Thr399Ile) and CD14 polymorphisms (base pair -159 and -260) with HBV-related cirrhosis in Chinese Han patients. By use of a polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis technique, we genotyped Toll-like receptor 4 (TLR4) Asp299Gly and Thr399Ile and CD14-159 and -260 polymorphisms in 110 HBV-related cirrhotic patients and 110 healthy controls from the Chinese Han population. We found significant differences in the genotypes and allele frequencies of CD14-159 (but not -260) between healthy controls and liver cirrhotic patients, and both the CD14-159 and -260 genotypes were significantly different among Child-Pugh grades in cirrhotic patients. No TLR4 Asp299Gly and Thr399Ile mutations were detected in any cirrhotic patients or healthy controls in the Chinese Han population. These findings indicated that the polymorphisms of CD14, but not TLR4 Asp299Gly and Thr399Ile mutations, may be an important genetic factor for HBV-related cirrhotic injury in the Chinese Han population.