Polymorphisms at position -308 in the promoter region of the TNF-alpha and in the first intron of the TNF-beta genes and spontaneous and lipopolysaccharide-induced TNF-alpha release in sarcoidosis.

TNF-alpha is a potent pro-inflammatory cytokine. Previous studies have proved that biallelic polymorphisms in the TNF-alpha (-308, TNFA) and TNF-beta genes (intron 1, TNFB) influence TNF-alpha production. In sarcoidosis, a chronic granulomatous disease, as a result of an unknown in vivo activation bronchoalveolar lavage (BAL) cells release high amounts of TNF-alpha, spontaneously and after in vitro stimulation. Thus, sarcoidosis could serve as a model to test the in vivo effect of TNF gene polymorphisms. We determined the TNFA and TNFB polymorphisms of 44 patients with sarcoidosis and found the following allele frequencies: 0.80, 0.20, 0.38 and 0.62 for TNFA1, TNFA2, TNFB1 and TNFB2, respectively. To examine the in vivo effect of the named polymorphisms on the TNF-alpha production, the spontaneous and LPS-induced TNF-alpha release of BAL cells and peripheral blood mononuclear cells were also determined in patients with sarcoidosis. Statistical analysis did not reveal any significant difference between sarcoidosis patients with different genotypes. The results show that TNFA and TNFB polymorphisms do not determine the level of TNF-alpha release of mononuclear cells activated during the course of sarcoid inflammation.     

Cytokine gene promoter polymorphisms and mortality in acute renal failure

BACKGROUND: Although cytokines play a pivotal role in the inflammatory responses that mediate the severity of acute renal failure (ARF), the importance of pro- and anti-inflammatory cytokine gene promoter polymorphisms has been unexplored. METHODS: We prospectively evaluated the relationship of single nucleotide polymorphism in the promoter region of tumor necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) to mortality in 61 patients with ARF requiring intermittent hemodialysis. Cytokine genotyping was performed on leukocytes using PCR techniques. Cox proportional-hazards regression analysis was used to explore these relationships. RESULTS: The mean (+/-SD) APACHE II score was 24 +/- 7, MOF score 2 +/- 1, and 64% had sepsis. The TNF-alpha high producer genotype (-308 A-allele carrier) was associated with a higher risk of death after adjustment for the APACHE II score (HR=2.5; P=0.04), and the IL-10 intermediate/high producer genotype (-1082 G-allele carrier) was associated with a lower risk of death after adjustment for the MOF score (HR=0.36; P=0.03). Considering combinations of genotypes, the TNF-alpha high and IL-10 low producer genotype combination was associated with a approximately 6-fold increased risk of death compared to the TNF-alpha-low and IL-10 intermediate/high producer genotype combination, after adjustment for either APACHE II (P=0.004), MOF score (P=0.004) or sepsis (P=0.006). CONCLUSIONS: TNF-alpha and IL-10 gene polymorphisms are related to the risk of death among patients with ARF who require dialysis. Larger studies are needed to confirm these relationships.     

Association between interleukin-6 polymorphism and age-at-onset of type 1 diabetes. Epistatic influences of the tumor necrosis factor-alpha and interleukin-1beta polymorphisms

Multiple immune mediators have been mentioned as playing a role in the pathomechanism of type1 DM. Interleukin (IL)-1beta, and tumor necrosis factor (TNF)-alpha play a central role in the autoimmune destruction of pancreatic beta-cells, whereas IL-6 inhibits TNF-alpha secretion, and may have some protecting effects. In our study, we aimed to investigate the association between these three cytokines' single nucleotide polymorphisms (IL-6 gene G(-174)C, TNF-alpha gene G(-308)A and IL-1beta gene C(3954)T polymorphisms) and age-at-onset of type 1 diabetes mellitus (T1DM) in 165 diabetic children (median age: 17 years). Polymorphisms were determined using the PCR-RFLP method. We found that the age-at-onset of T1DM was significantly different in patients with a different IL-6 genotype (median age-at-onset of T1DM was: 8, 6 and 4.5 years in children with the (-174)GG, GC and CC genotypes, respectively; p < 0.01). Adjusted for TNF-alpha and IL-1beta polymorphisms, patients with a IL-6 (-174)CC genotype have a 3.0-fold (95% CI: 1.2-7.1) increased risk of developing diabetes before the age of 6 years than (-174)G allele carrier patients. However, we found this association to be present only in patients who carried the TNF-alpha (-308)A or IL-1beta (3954)T allele, i.e. in patients with high TNF-alpha and high IL-1beta producer genotypes. We suppose that in the case of high TNF-alpha and IL-1beta producer genotypes, elevated proinflammatory cytokine levels result in a higher production of IL-6 in (-174)G allele carrier patients. This elevated IL-6 level may have a protective effect against the development of T1DM and may delay the destruction of pancreatic beta-cells.     

The Association of IL28B Polymorphism and Graft Survival in Patients with Hepatitis C Undergoing Liver Transplantation

Hepatitis C virus (HCV) infection is the leading cause of liver transplantation (LT) in Western countries. Polymorphism in the IL28B gene region has a major impact on the natural history and response to antiviral treatment in HCV. We investigated whether IL28B polymorphism was associated with graft survival in patients with or without HCV undergoing LT. 1,060 adult patients (age >18 years) underwent LT between years 2000 and 2008. Patients with previous LT, living donor LT and patients dying or requiring retransplants within 30 days of LT were excluded. DNA samples of 620 (84%) recipients and 377 (51%) donors were available for genotyping of IL28B rs12979860C>T. Donor IL28B genotypes had no significant differences in graft survival irrespective of HCV status. There was no difference in graft outcome in the non-HCV cohort (n = 293) based on recipient IL28B genotype. In the HCV group (n = 327), recipients with CC or CT genotype had better graft survival compared to TT genotype (62% vs. 48%, p = 0.02). HCV recipients with CC or CT genotype had delayed time to clinically relevant HCV recurrence compared to TT (10.4 vs. 6.7 months, p = 0.002). The beneficial effect of the CC/CT genotype on HCV recurrence and graft survival was independent of antiviral treatment. In conclusion, our study demonstrated that in contrast to donor IL28B genotype recipient IL28B was associated with graft survival and clinically relevant HCV recurrence in HCV infected recipients. No effect of IL28B genotype was manifest in non-HCV LT recipients.     

<Emphasis Type="Italic">TNF</Emphasis><Emphasis Type="Italic">α</Emphasis> and <Emphasis Type="Italic">LT</Emphasis><Emphasis Type="Italic">α</Emphasis> gene polymorphisms as additional markers of celiac disease susceptibility in a DQ2-positive population

TNFalpha and TNFbeta, or linfotoxin (LTalpha), are two molecules playing an important role in inflammation. Their genes map on Chromosome 6, between the HLA class II and class I loci. Polymorphisms in, or near, TNF genes have been associated with susceptibility to several autoimmune diseases. Studies of TNF genes in celiac disease (CD) have presented contradictory results. We have assessed the role of TNFalpha and linfotoxin alpha (TNFbeta) in CD and their relative value as CD markers in addition to the presence of DQ2. The TNFA -308 polymorphism and the polymorphism at the first intron of the LTA gene were typed in CD patients and healthy controls and the results were correlated with the presence of DQ2. Significant differences were found in genotype and allele frequencies for the TNFA and LTA genes between CD patients and controls, with an increase in the presence of the TNFA*2 and LTA*1 alleles in CD patients. These differences increase when DQ2-positive CD patients and DQ2-positive controls are compared. In DQ2-positive individuals, allele 2 (A) in position -308 of the promoter of TNFA and allele 1 (G) of the NcoI RFLP in the first intron of LTA are additional risk markers for CD.     

Meta-analysis identified the TNFA -308G > A promoter polymorphism as a risk factor for disease severity in patients with rheumatoid arthritis

Introduction

The goal of this study is to investigate whether the -308G > A promoter polymorphism in the tumor necrosis factor alpha (TNFA) gene is associated with disease severity and radiologic joint damage in a large cohort of patients with rheumatoid arthritis (RA).

Methods

A long-term observational early RA inception cohort (n = 208) with detailed information about disease activity and radiologic damage after 3, 6 and 9 years of disease was genotyped for the TNFA -308G > A promoter polymorphism (rs1800629). A longitudinal regression analysis was performed to assess the effect of genotype on RA disease severity and joint damage. Subsequently, a meta-analysis, including all publically available data, was performed to further test the association between joint erosions and the TNFA polymorphism. To learn more about the mechanism behind the effect of the polymorphism, RNA isolated from peripheral blood from RA patients (n = 66) was used for TNFA gene expression analysis by quantitative PCR.

Results

Longitudinal regression analysis with correction for gender and disease activity showed a significant difference in total joint damage between GG and GA+AA genotype groups (P = 0.002), which was stable over time. The meta-analysis, which included 2,053 patients, confirmed an association of the genetic variant with the development of erosions (odds ratio 0.78, 95% CI 0.62, 0.98). No significant differences in TNFA gene expression were observed for the different genotypes, confirming earlier findings in healthy individuals.

Conclusions

Our data confirm that the TNFA -308G > A promoter polymorphism is associated with joint damage in patients with RA. This is not mediated by differences in TNFA gene expression between genotypes.     

Analysis of CYP1A1 exon 7 polymorphisms by PCR-SSCP in a Brazilian population and description of two novel gene variations

CYP1A1 polymorphisms have been associated with a higher risk to develop lung cancer, particularly in Japanese. The type and the frequency of the polymorphisms can vary according to the ethnicity. In the present study, we aimed to determine the frequency of CYP1A1(*)2B and (*)4, and to look for other possible polymorphisms that may happen in exon 7 in individuals from Rio de Janeiro, an ethnic mixed population from Brazil. We developed a PCR-SSCP method for screening the genomic polymorphic region from 2289 to 2645 bp. Seven different migration patterns were found among 405 individuals, 130 healthy blood donors and 275 outpatients from Hospital Universitário Pedro Ernesto located in Rio de Janeiro. Five of the migration patterns corresponded to the genotypes: (*)1/(*)1 (the wild type); (*)1/(*)2B; (*)1/(*)4, (*)2B/(*)4 (heterozygous polymorphic) and (*)2B/(*)2B (homozygous polymorphic). Two other patterns corresponded to gene alterations not yet published: a C > T transition localized at the position 2461, and a C > T transition localized at position 2445. The genotype frequencies of the studied polymorphisms were: for CYP1A1(*)2B - 83.7% to (*)1/(*)1, 15.1% to (*)1/(*)2B and 1.2% to (*)2B/(*)2B; for CYP1A1(*)4 - 93.1% to (*)1/(*)1, 6.9% to (*)1/(*)4. The distribution of CYP1A1(*)2B and (*)4 genotypes combined were similar between white and non-white individuals. However, when the non-white individuals were stratified between blacks and mulattos, and then compared with white, black individuals showed a higher frequency of the wild type genotype (P = 0.008) and a lower frequency of genotype (*)1/(*)4 (P = 0.026). Additionally, when black and mulatto individuals were compared, blacks had a higher frequency of the wild type genotype (P = 0.008) and a lower frequency of the(*)1/(*)2B genotype (P = 0.0008), showing a different ethnic distribution of CYP1A1 polymorphisms.     

Analysis of IL-1A(-889) and TNFA(-308) gene polymorphism in Brazilian patients with generalized aggressive periodontitis

Generalized aggressive periodontitis (GAP) comprises a group of periodontal diseases characterized by the rapid destruction of periodontal tissues which affect young individuals who generally present no systemic disorders. Polymorphisms in the interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) genes have been associated with an increased severity of chronic periodontitis. The objective of the present study was to evaluate the association between IL-1A (-889) and TNFA (-308) gene polymorphisms and GAP. One hundred nonsmoking subjects were selected, including 30 with GAP and 70 without periodontal disease. Gene polymorphisms were analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. For IL-1 (-889), the frequency of genotype 1/1 was 54.3% in the control group and 56.7% in the study group. The frequency of genotype 1/2 was 37.1% in the control group and 40% in the study group. Genotype 2/2 was detected at a frequency of 8.6% and 3.3% in the control and study groups, respectively. For TNFA, genotype 1/1 was present in 68.6% of control subjects and in 80.0% of patients with GAP, while the frequency of genotype 1/2 was 27.1% in the control group and 20% in the study group. Genotype 2/2 was present in 4.3% of control subjects and was not detected in the study group. The frequencies of allele 1 and allele 2 of the IL-1A (-889) gene were 72.9% and 27.1%, respectively, in the control group and 76.7% and 23.3% in the GAP group. For the TNFA (-308) gene, the frequency of allele 1 was 82.15% in the control group and 90% in the study group, whereas the frequency of allele 2 was 17.85% in the control group and 10% in the study group. Statistical analysis revealed no significant difference in allele distribution for either gene between the two groups. No association was observed between GAP and IL-1A (-889) and TNFA (-308) gene polymorphisms in Brazilian patients.     

Pyrosequencing to Identify Homogeneous Phenomenon When Using Recipients/Donors with Different CYP3A5*3 Genotypes in Living Donor Liver Transplantation

This study used pyrosequencing to determine the proportional distribution of CYP3A5*3 genotypes to further confirm the homogeneous phenomenon that is observed when recipients and donors in living donor liver transplantation (LDLT) have a different single nucleotide polymorphism (SNP) genotype. We enrolled 42 recipient/living donor pairs and the SNPs of CYP3A5*3 were identified by polymerase chain reaction-restriction fragment length polymorphism. We performed 120 liver graft biopsies as part of clinical investigations after LDLT. Pyrosequencing of the CYP3A5*3 SNPs revealed that among the 16 recipients with the G/G genotype, 94.68% had the G and 5.32% the A allele. Among the 14 recipients with the A/G genotype, 78.08% had the G and 21.92% the A allele, and among the 12 recipients with the A/A genotype, 18.45% had the G and 81.55% the A allele. Among the 12 donors with the G/G genotype, 93.85% had the G and 6.14% the A allele. Among the 26 donors with the A/G genotype, 75.73% had the G and 24.27% the A allele, and among the 4 donors with the A/A genotype, 11.09% had the G and 88.91% the A allele. There were a total of 120 liver graft biopsy samples; among the 37 recipients with the G/G genotype, 89.74% had the G and 10.26% the A allele, among the 70 recipients with the A/G genotype, 71.57% had the G and 28.43% the A allele, and among the 13 recipients with the A/A genotype, 48.25% had the G and 51.75% the A allele. The proportional distribution of G and A alleles of the CYP3A5*3 SNP between recipients/donors and liver grafts after LDLT was significantly different (p<0.001). Pyrosequencing was useful in identifying detailed proportional changes of the CYP3A5*3 SNP allele distribution, and to confirm the homogeneous phenomenon when recipients and donors in LDLT have a different genotype.     

Cytochrome P450 in living donor liver transplantation

Cytochrome P450 metabolizes many drugs in the liver. Three genotypes of CYP2C19 with extensive, intermediate, and poor metabolizing activity, respectively, have been identified in peripheral blood of transplant recipients and new liver grafts in living donor liver transplantation (LDLT). The expression of the final genotype in liver graft biopsies depends on the donor, whereas the expression in peripheral blood mononuclear cells depends on the recipient. The metabolizing isoenzyme of the major anti-rejection agents passes through CYP3A4, CYP3A5 and MDR1, which have also been identified to have similar biological characteristics as genotype of CYP2C19 in liver tissue. Recently, pyrosequencing has been used to investigate the expressions of different genotypes in liver grafts in LDLT. This review focuses on recent findings regarding the biological expressions of the CYP2C19, CYP3A4, CYP3A5 and MRD1 genotypes in liver grafts before and after LDLT. The application of pyrosequencing may be beneficial in further research on liver transplantation. Laser capture microdissection of hepatocytes in liver grafts may be a direction for future research.     

Angiotensinogen,angiotensine converting enzyme and plasminogen activator inhibitor-1 gene polymorphism in chronic allograft dysfunction

Despite dramatic improvements in first-year patient and graft survival rates, chronic allograft dysfunction (CAD) remains the leading cause of late renal allograft loss, while current immunologic strategies have little effect on this condition. The renin–angiotensin system (RAS) plays an important role in progression of chronic renal disease. It was shown that plasminogen activator inhibitor-1 (PAI-1) functions in the RAS. This study investigates the possible links between angiotensinogen (AGT M235T), angiotensin-converting enzyme (ACE) and PAI-1 genotypes with CAD. Assessments of polymorphism were performed in 127 renal allograft recipients (77 with CAD and 50 with normal renal function). Fifty healthy subjects were also considered for comparison. Genotypes were determined using polymerase chain reaction (PCR) sequence-specific primers and PCR followed by restriction fragment length polymorphism analysis. Kidney recipients with CAD had significantly higher frequencies of the TT than the recipients without CAD (P < 0.05). The transplant recipients with CAD also had significantly higher frequencies of the DD genotype than those without CAD (P < 0.05). No significant differences were observed between the allelic and genotypic distributions of PAI-1 polymorphisms. Therefore, determination of AGT M235T and ACE genotypes prior to transplantation may be useful to identify patients who are at risk for chronic renal transplant dysfunction.     

Involvement of interaction between viral VP466 and host tropomyosin proteins in virus infection in shrimp

The C3 component of complement has different roles in kidney disease and its local production in donor kidney may affect allograft function and rejection after organ transplantation. A single base substitution in c3 gene (rs2230199), defines two common allelic variants with different mobility on gel electrophoresis: S (Slow) and F (Fast). In order to evaluate the effect of this polymorphism on acute renal allograft rejection, one hundred samples of donor and recipients were collected and genotyping was done by PCR-RFLP method. The allelic frequencies were: C3S=0.791, C3F=0.209. There was no significant association between recipient's genotype and acute rejection (p value<0.05). No correlation between donor genotype and acute rejection was also present. Patients were divided into four groups, according to the recipient and donor genotypes: SS recipients and FS or FF donor, SS recipient and donor, FF or FS recipient and SS donor and FS or FF recipient and donor. There was no significant difference in rate of acute rejection between groups. Although the results didn't find any association between C3 complement polymorphisms and acute allograft rejection, there was no acute rejection in FS or FF donors and SS recipient group.     

猪乳中一组高分子量蛋白的多态性与乳生长因子、窝增重的关系

利用十二烷基硫酸钠-聚丙烯酰胺凝胶不连续垂直板电泳(SDS-PAGE),对162头二花脸母猪乳中一组高分子量蛋白质(HMWP)进行了检测和分型,并运用线型模型统计分析方法分析了该基因座的不同基因型与母猪的乳生长因子(IGF-1、EGF和胰岛素)、哺乳仔猪生长(20日龄窝增重)的关系.结果表明,在三种HMWP基因型中,不同基因型母猪的乳中IGF-1浓度存在显著差异,HMWP基因型为BB型和BD型的母猪,其乳IGF-1浓度均高于DD型,其中BB型显著高于DD型(P＜0.05).乳中胰岛素浓度也存在差异的趋势,但未达到显著水平(P＞0.05),BB型和BD型母猪的乳中胰岛素浓度高于DD型.HMWP基因座不同基因型的乳EGF浓度无显著差异(P＞0.05).在三种HMWP基因型中,不同基因型母猪的20日龄窝增重存在显著差异,HMWP基因座为BB型和BD型的母猪,其20日龄窝增重均高于DD型,其中BD型显著高于DD型(P＜0.05).实验结果提示,HMWP多态性可能作为一个潜在的遗传标记应用于猪的遗传育种.     

Allelic variants of the tumor necrosis factor superfamily as markers of the severity of the course of chronic obstructive lung disease and bronchiectatic disease

The distribution of allelic variants of genes of the TNF superfamily (TNFA and LTA) was studied in 172 patients with chronic obstructive pulmonary disease (COPD), bronchiectatic disease (n = 22), and in healthy individuals (n = 169). Analysis of the TNFA gene locus -308G-->A revealed no differences between the examined groups. Analysis of the LTA gene polymorphic locus +252A-->G showed that in patients with COPD, the frequency of the G allele was significantly higher than that in the control group (chi 2 = 3.98, p < 0.05). The presence of this allele in the genotype was correlated with the degree of COPD severity. Thus, in patients with stage II COPD, heterozygous AG genotype predominated (51.3%), whereas in patients with stage III COPD, the frequency of AG genotype was reduced to 32.7% at the expense of increased frequency of GG genotype (14.6%) (chi 2 = 6.78, p < 0.05; OR = 4.6, CI 1.37-15.96). The distribution of combined TNFA and LTA genotypes was also studied. In the group of COPD patients, the proportion of individuals with a combination of normal GG TNFA genotype and heterozygous AG LTA genotype was significantly higher (28.5% versus 18.4% in control; chi 2 = 4.14, p < 0.05; OR = 1.75, CI = 1.01-3.04). Genotype combinations were characterized at various clinical stages of COPD and bronchiectatic disease (BED). Thus, we have shown for the first time ever that LTA gene alleles and their combinations with the polymorphic variants of the TNFA gene are associated with predisposition to COPD and severity of this disease.     

Influence of glutathione<Emphasis Type="Italic"> S</Emphasis>-transferase M1 and T1 polymorphisms with acute rejection in Iranian liver transplant recipients

Glutathione-S-transferase (GST) has a major protective role against free radicals and plays a vital role in phase II of biotransformation of many substances. In liver transplantation, reperfusion injury, calcineurin drug consumption and infection produce free radicals that cause tissue injury and organ damage. Genetic variations of GST may influence individual susceptibility to some diseases associated with the deleterious effects of oxidative metabolism. Although it is well known that the rejection is an immunological process, however, in this study, we have investigated the gene frequency and relationship between human GST gene polymorphism and rejection in liver transplant recipients. We have assessed 51 liver transplant recipients from Shiraz, South of Iran. The GSTT1 and GSTM1 genotypes were identified by polymerase chain reaction (PCR). The gene frequency of GSTM1 and GSTT1 polymorphism were evaluated. We observed that GSTM1 null genotype was present in 68.62% of the liver transplant recipients while GSTT1 null genotype was present in 37.25% of the liver transplant subjects. There was a trend between increasing age and acute rejection episode. No statistically significant correlation was present between GSTM1 null and GSTT1 null genotypes with an acute rejection episode in transplant recipients. No relationship was observed between GST genotypes and acute rejection. It is likely that development and progression of rejection are determined by genes which is involved in immunological pathways rather than genes that is participated in free radicals destruction. However, these findings need to be confirmed in a larger series of patients.     

Association of immune system gene polymorphisms with quantitative features which are pathogenetically important in chronic viral hepatitis

Association study was performed for genetic polymorphisms IL4 C(-590)T, IL4RA Ile50Val, TNF G(-308)A, to estimate their effect on quantitative features which are pathogenetically important for chronic viral hepatitis course, i.e. levels of IL4, IL10, IL12, tumor necrosis factor alpha, fibronectin, collagenase, protease inhibitors, macroglobulines, elastases, free and protein-bound hydroxyproline. It has been shown that A allele of TNF G(-308)A polymorphism is associated with decreased TNF-alpha, increased IL4 and IL12, as well as with low level of protein-bound hydroxyproline. In addition, association of CT genotype of IL4 C(-590)T polymorphism and high level of protein-bound hydroxyproline has been identified.     

Genetic polymorphisms in patients with myelodysplastic syndrome

Myelodysplastic syndrome (MDS) is a family of clonal disorders characterized by dyshematopoiesis and susceptibility to acute myelogenous leukemia. Tumor necrosis factor-a (TNF-alpha) and transforming growth factor-beta (TGF-beta) are cytokines that play key roles in the pathogenesis of MDS. There have been several reports on the presence of genetic polymorphisms in the DNA sequence encoding the leader sequence of the TGF-beta protein, and in the -308 promoter region of TNF-alpha. The association between TNF-alpha and TGF-beta1 gene polymorphism and the susceptibility to MDS and the progression of the disease was investigated. As compared with healthy control subjects (n = 74), patients with MDS (n = 55) showed no significant deviations in genotype or allele frequencies of TNF-alpha. Similarly, there were no differences in the distribution of TNF-alpha genotypes between the MDS patients with only anemia (mild group) and those with bi- or pancytopenia (severe group). On the other hand the TT homozygosity at codon 10 in exon 1 of TGF-beta1 gene was associated with a severe degree of cytopenia [95% CI OR = 4.889, p = 0.0071]. These findings suggest that the investigated genetic polymorphisms do not predispose to the development of MDS, but that TGF-beta1 gene polymorphism may affect the disease progression.     

TNF gene polymorphisms are associated with reduced survival in severe Chagas' disease cardiomyopathy patients

Chronic Chagas' disease cardiomyopathy (CCC) is the most important clinical outcome of infection by the parasite Trypanosoma cruzi, affecting 18 million individuals in Latin America. One-third of CCC patients develop heart failure due to end-stage dilated cardiomyopathy, and their survival is reduced by 50% compared to patients with other cardiomyopathies. Genetic susceptibility may play a role in the differential survival of severe CCC patients. Given the role of TNF-alpha in the progression of heart failure, and the increased TNF-alpha plasma and heart tissue levels observed in these patients, we chose TNF as a candidate gene for increased mortality in severe CCC patients. We typed the TNFa microsatellite and the -308 TNF promoter polymorphism and then analyzed the survival curves of 42 patients with severe ventricular dysfunction (left ventricular ejection fraction相似文献   

Genetic variation in the cannabinoid receptor gene (CNR1) (G1359A polymorphism) and their influence on anthropometric parameters and metabolic parameters under a high monounsaturated vs. high polyunsaturated fat hypocaloric diets

An intragenic polymorphism (1359 G/A) of the cannabinoid receptor 1 (CNR1) gene was reported as a common polymorphism in Caucasian populations (rs1049353). Intervention studies with this polymorphism have yield contradictories results. We decide to investigate the role of polymorphism (G1359A) of (CNR1) gene on metabolic parameters and weight loss secondary to a high monounsaturated fat and high polyunsaturated fat hypocaloric diets in obese subjects. A population of 258 obese subjects was analyzed in a randomized trial. A nutritional evaluation was performed at the beginning and at the end of a 3-month period in which subjects received 1 of 2 diets (diet M: high monounsaturated fat diet vs diet P: high polyunsaturated fat diet). One hundred and sixty five patients (63.9%) had the genotype G1359G and 93 (36.1%) patients (A allele carriers) had G1359A (78 patients,30.3%) or A1359A (15 patients,5.8%) genotypes. In subjects with both genotypes, body mass index, weight, fat mass, waist circumference and systolic blood pressures decreased with both diets. With the diet-type M and in both genotype groups, biochemical parameters remained unchanged. After the diet type P and in subjects with both genotypes, glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, insulin and homeostasis model assessment for insulin resistance (HOMA-IR) levels decreased. In G1359G genotype subjects after both diets, leptin levels decreased. The finding of this study is the association of the A allele with a lack of improvement on leptin levels. Subjects with both genotypes and after a high polyunsaturated fat hypocaloric diet showed a significant improvement of LDL cholesterol, total cholesterol, HOMA-IR and insulin levels.