Transforming Growth Factor-β1 Gene Polymorphisms Research Articles

Transforming growth factor-β1 gene polymorphism as a potential risk factor in Turkish patients with laryngeal squamous cell carcinoma.

Laryngeal cancer is the most common head-and-neck malignancies with more than 20% of all cases. The vast majority of tumors are squamous cell carcinoma (SCC). Several genes encoding different cytokines may play crucial roles in host susceptibility to cancer because cytokine production capacity varies among individuals and depends on cytokine gene polymorphisms. The association between cytokine gene polymorphisms with primary laryngeal SCC was investigated. DNA samples were obtained from a Turkish population of eighty patients with primary cancer and fifty healthy controls. All genotyping (interferon-gamma, transforming growth factor-β1 [TGF-β1], tumor necrosis factor-alpha [TNF-α], interleukin [IL]-6, and IL-10) experiments were performed using polymerase chain reaction sequence-specific primers. When compared to the healthy controls, the frequencies of TGF-β1 codon 25 (rs1800471) GC genotype and 25 C allele were significantly more common in the patient group. These results suggest that TGF-β1 gene polymorphisms may affect host susceptibility to laryngeal cancer.

The Role of Transforming Growth Factor-β1 Gene Polymorphism and Its Serum Levels in Hashimoto's Thyroiditis.

TGF-β1 gene (TGFB1) is one of the target genes involved in genetic predisposition to autoimmune diseases, particularly Hashimoto's thyroiditis (HT). In the present study, we attempted to investigate whether -509C/T SNP (rs1800469) in the promoter of TGFB1 is associated with the genetic susceptibility and clinical characteristics of Bulgarian patients with HT. We also analyzed serum TGF-β1 levels in different stages of the disease and its association with the -509C/T polymorphism in the TGFB1 promoter. The study recruited 121 female out-patients with autoimmune thyroiditis and 250 agematched healthy women (HC). Genotyping of the rs1800469 was performed by restriction fragment length polymorphism (RFLP)-PCR assay. The serum concentrations of latent acid-activated TGF-β1 protein were determined by the quantitative sandwich ELISA method. Upon testing different types of inheritance, a significant risk was found for heterozygotes (CT) with OR=1.640; p=0.05 under the codominant model. The significantly higher risk for developing Hypothyroidism was calculated again for CT-genotype patients with OR=1.789. According to the hormone reference values, a significant association of CT genotype with decreased TSH (75.4%) simultaneously with increased free T4 hormone (94%) levels was also calculated. When patients were stratified by genotype and compared to the same genotype in HC, we observed that the decreased levels in serum TGF-b1 were significant for patients who carried the C-allele in their genotype. We suggest that heterozygous genotype CT is a genetic risk factor for developing more severe HT due to enhanced free T4 serum level at the onset of the disease, before developing the hypothyroid stage.

Transforming growth factor-β1 gene polymorphisms with liver cirrhosis risk: A meta-analysis

Although several epidemiological studies have investigated the association of transforming growth factor-β1 (TGF-ß1) gene polymorphisms with the susceptibility to liver cirrhosis (LC), controversial results exist. Consequently, we performed a meta-analysis to accurately evaluate the relationship of TGF-ß1-509C/T and codon 10T/C polymorphisms with the risk of LC introduced by chronic hepatitis B/V virus (HBV/HCV) infection. A total of 9 case-control studies, involving 985 LC patients and 909 controls, were recruited for meta-analysis. The results suggested a significant association between the -509C/T polymorphism and LC risk in the total population. Stratification by ethnicity revealed similar associations in Egyptian and Caucasian populations, but not in Asian populations. Subgroup analyses by different etiologies also showed similar associations in HCV-induced LC, but not in HBV-induced LC. However, the overall data failed to show a significant association between codon 10T/C polymorphism and the risk of LC in the study. We concluded that TGF-ß1-509C/T polymorphism was significantly associated with LC susceptibility, while the codon 10T/C polymorphism seemed to have a limited role in predicting the occurrence of LC induced by HBV/HCV infection.

Transforming Growth Factor-β1 gene polymorphism and osteoporosis in postmenopausal egyptian women.

Transforming growth factor-β1 (TGF-β1) is a wide spread bone matrix protein that affect the function, formation and cell-cell interactions of osteoclasts and osteoblasts to regulate bone remodeling and sustain adequate bone mass. The aim of this study is to evaluate the role of the two polymorphism of transforming growth factor-β1 T869C and C-509T in developing osteoporosis in postmenopausal Egyptian women. This study was performed on 138 postmenopausal osteoporosis/osteopenic women and 128 postmenopausal female control group. There was a significant statistical difference in the CC, CT and TT (T869C) genotype frequencies between the osteopenia/osteoporosis and control subjects (p value <0.001). There was a non-significant statistical difference in the CC, CT and TT (T-509C) genotype frequencies between the osteopenia/osteoporosis and control subjects (p value <0.082). There was a significant statistical difference between TT,CT and CC of (T869C) and T score, Z score and calcium of osteopenia/osteoporosis group (p value <0.001). There was a non-significant statistical difference between TT, CT and CC of (T-509C) and T score, Z score of osteopenia/osteoporosis group (p value 0.32,0.31),but there was a statistically significant difference between the three genotyping and serum calcium and creatinine (p value 0.04). Multivariate regression analysis showed that T869C polymorphism is a significant risk factor for osteopenia/ osteoporosis (OR 3.57, 95% CI= 1.56-5.67). We concluded that T869C polymorphism of the TGF-β1 gene has an impact on bone mineral density and enhancement of the susceptibility to osteopenia/osteoporosis in Egyptian women.

Transforming Growth Factor-β1 T869C Gene Polymorphism Is Associated with Acquired Sick Sinus Syndrome via Linking a Higher Serum Protein Level

BackgroundFamilial sick sinus syndrome is associated with gene mutations and dysfunction of ion channels. In contrast, degenerative fibrosis of the sinus node tissue plays an important role in the pathogenesis of acquired sick sinus syndrome. There is a close relationship between transforming growth factor-β1 mediated cardiac fibrosis and acquired arrhythmia. It is of interest to examine whether transforming growth factor-β1 is involved in the pathogenesis of acquired sick sinus syndrome.MethodsOverall, 110 patients with acquired SSS and 137 age/gender-matched controls were screened for transforming growth factor-β1 and cardiac sodium channel gene polymorphisms using gene sequencing or restriction fragment length polymorphism methods. An enzyme-linked immunosorbent assay was used to determine the serum level of transforming growth factor-β1.ResultsTwo transforming growth factor-β1 gene polymorphisms (C-509T and T+869C) and one cardiac sodium channel gene polymorphism (H588R) have been identified. The C-dominant CC/CT genotype frequency of T869C was significantly higher in acquired sick sinus syndrome patients than in controls (OR 2.09, 95% CI 1.16–3.75, P = 0.01). Consistently, the level of serum transforming growth factor-β1 was also significantly greater in acquired sick sinus syndrome group than in controls (5.3±3.4 ng/ml vs. 3.7±2.4 ng/ml, P = 0.01). In addition, the CC/CT genotypes showed a higher transforming growth factor-β1 serum level than the TT genotype (4.25 ± 2.50 ng/ml vs. 2.71± 1.76 ng/ml, P = 0.028) in controls.ConclusionTransforming growth factor-β1 T869C polymorphism, correlated with high serum transforming growth factor-β1 levels, is associated with susceptibility to acquired sick sinus syndrome.

Investigation of Transforming Growth Factor-β1 Gene Polymorphisms Among Iranian Patients With Chronic Hepatitis C

: Background: Chronic hepatitis C infection is caused by the hepatitis C virus (HCV), and its clinical complications include liver cirrhosis, liver failure, and hepatocellular carcinoma. Transforming growth factor-β1 (TGF-β1) is an important cytokine in cell growth and differentiation, angiogenesis, extracellular matrix formation, immune response regulation, and cancer development and progression.Objectives: The aim of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) in TGF-β1 and chronic HCV infection among patients referred to the Taleghani Hospital, Tehran, Iran between 2008 and 2010.Patients and Methods: In this case-control study, samples were collected using a convenience sampling method. We genotyped 164 HCV patients and 169 healthy controls for 3 SNPs in the TGF-β1 gene (-509 promoter, codon 10, and codon 25). We determined the SNP genotypes by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. To confirm the PCR-RFLP genotyping results, 10% of the samples were re-genotyped using a direct sequencing method.Results: There were no significant differences in the allelic frequency distribution of SNPs at -509 C/T, +869 C/T, or +915 G/C between HCV patients and the healthy controls. Genotyping results for all three polymorphic sites were similar with no statistically significant differences between the groups.Conclusions: Most of the Iranian patients (over 85%), both healthy controls and HCV patients, had the GG genotype at the +915 G/C position, resulting in a high level of TGF-β1 production. Therefore, we concluded that the SNPs investigated by us cannot be considered as prognostic factors for HCV infection in our population, despite being reported as prognostic markers in other populations. Moreover, there is a possibility that most of the population is susceptible to HCV infection. Implication for health policy/practice/research/medical education: Transforming growth factor beta-1 (TGF-β1) is a multifunctional cytokine that acts as a regulator of proliferation and cellular differentiation.Investigation of the association of single nucleotide polymorphisms (SNPs) in TGF-β1 gene sequence with increased or decreased individual’s susceptibility to chronic diseases such as hepatitis C infection could be helpful to find appropriate and population specific genetic biomarkers. Please cite this paper as: Romani S, Azimzadeh P, Mohebbi SR, Kazemian S, Almasi S, Naghoosi H, et al. Investigation of Transforming Growth Factor–β1 Gene Polymorphisms Among Iranian Patients With Chronic Hepatitis C. Hepat Mon. 2011;11(11):901-6. DOI: 10.5812/kowsar.1735143X.776

Investigation of Transforming Growth Factor-β1 Gene Polymorphisms Among Iranian Patients With Chronic Hepatitis C

Chronic hepatitis C infection is caused by the hepatitis C virus (HCV), and its clinical complications include liver cirrhosis, liver failure, and hepatocellular carcinoma.Transforming growth factor-β1 (TGF-β1) is an important cytokine in cell growthand differentiation, angiogenesis, extracellular matrix formation, immune responseregulation, and cancer development and progression. The aim of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) in TGF-β1 and chronic HCV infection among patients referred to the Taleghani Hospital, Tehran, Iran between 2008 and 2010. In this case-control study, samples were collected using a convenience sampling method. We genotyped 164 HCV patients and 169 healthy controls for 3 SNPs in the TGF-β1 gene (-509 promoter, codon 10, and codon 25). We determined the SNP genotypes by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. To confirm the PCR-RFLP genotyping results, 10% of the samples were re-genotyped using a direct sequencing method. There were no significant differences in the allelic frequency distribution of SNPs at -509 C/T, +869 C/T, or +915 G/C between HCV patients and the healthy controls. Genotyping results for all three polymorphic sites were similar with no statistically significant differences between the groups. Most of the Iranian patients (over 85%), both healthy controls and HCV patients, had the GG genotype at the +915 G/C position, resulting in a high level of TGF-β1 production. Therefore, we concluded that the SNPs investigated by us cannot be considered as prognostic factors for HCV infection in our population, despite being reported as prognostic markers in other populations. Moreover, there is a possibility that most of the population is susceptible to HCV infection.

Transforming Growth Factor-β1 Gene Polymorphisms in Korean Women With Endometriosis

To investigate the association between endometriosis, transforming growth factor-β1 (TGFB1) gene polymorphisms, and serum TGF-β1 levels in Korean women. The -509C/T, 868T/C, 913G/C and 979G/A polymorphisms of the TGFB1 gene were analyzed in women with (n = 131) and without (n = 107) endometriosis using restriction fragment length polymorphism (RFLP) analysis. Serum TGF-β1 levels were measured by enzyme-linked immunosorbent assay (ELISA). The 913G/C and 979G/A polymorphisms were not observed in the study participants. The genotype and allele distribution of the -509C/T and 868T/C polymorphisms in endometriosis were similar to those in controls. However, the -509T/868C (TC) haplotype allele was observed 4.55 times more frequently in early-stage endometriosis than in other haplotype alleles. Serum TGF-β1 levels were significantly higher in endometriosis than in controls. The single and haplotype genotype of -509C/T and 868T/C polymorphisms were not related with serum TGF-β1 levels. The TC haplotype allele of TGFB1-509C/T and 868T/C polymorphisms may be associated with early-stage endometriosis in Korean women.

Association of interleukin-6 and transforming growth factor-β1 gene polymorphisms with developmental hip dysplasia and severe adult hip osteoarthritis: A preliminary study

Developmental hip dysplasia (DDH) greatly contributes to occurrence of severe hip osteoarthritis (OA) in adulthood, but the association between the two is not a perfect one. Both conditions are known to have a strong genetic component. Transforming growth factor β1 (TGF-β1) and interleukin-6 (IL-6) are two pro-inflammatory cytokines included in pathogenesis of OA, bone remodeling and development of bone and joint tissues. TGF-β1 gene has a polymorphic site in the signal sequence (29T→C) and “C allele carriage” is associated with higher circulating TGF-β1 levels. IL-6 gene has several polymorphic sites in the promoter region including −572T→C transition associated with higher circulating IL-6 levels. As a preliminary investigation on possible association between these polymorphisms and severe adult hip OA secondary to DDH, 28 consecutive patients and 20 healthy controls were genotyped at these loci. With adjustment for sex, “C allele carriage” in the TGF-β1 signal sequence and CC genotype (“transition homozygous”) at locus −572 in the IL-6 promoter were each associated with severe OA secondary to DDH (OR=13.4, p=0.016 and OR=6.2, p=0.024, respectively). The combination of these genotypes was particularly strongly associated with the disease (OR=11.1, p<0.001). Data support feasibility of larger-scale studies on potential association between TGF-β1 signal sequence and IL-6 promoter polymorphisms and occurrence of DDH and (un)related severe OA.

Association of transforming growth factor-β1 gene polymorphisms with genetic susceptibility to nasopharyngeal carcinoma

Background Nasopharyngeal cancer (NPC) is multifactorial, and the genetic background may be a crucial etiologic factor. Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine, it promotes tumor growth and metastasis in later stages of phase of cancer development. Variations in the DNA sequence in the TGF-β1 gene may lead to altered TGF-β1 production and/or activity, and so this can modulate an individual's susceptibility to NPC. To test this hypothesis, we investigated the association of the TGF-β1 polymorphisms and their haplotypes with the risk of NPC in a Chinese population. Methods We analyzed 2 single nucleotide polymorphisms (SNPs) of TGF-β1 gene promoter − 509C/T and 869T/C (Leu10Pro) at exon one in 108 patients with NPC and 120 age- and sex-matched controls in a Chinese population, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) strategy. Results There were significant differences in the genotype and allele distribution of − 509C/T and 869T/C (Leu10Pro) polymorphisms of the TGF-β1 gene among cases and controls. The − 509T and 869C alleles carriers were associated with a significantly increased risk of NPC as compared with the non-carriers (OR = 1.64, 95% CI, 1.13−2.39, P = 0.009 and OR = 1.70, 95% CI, 1.17−2.46, P = 0.006, respectively). Consistent with the results of the genotyping analyses, the − 509T/869C haplotype was associated with a significantly increased risk of NPC as compared with the − 509C/869T haplotype (OR = 1.68; 95% CI, 1.14−2.48; P = 0.009). Conclusion TGF-β1 − 509C/T and 869T/C polymorphisms, and their haplotypes are significantly associated with the risk of NPC. Our data suggests that TGF-β1 − 509C/T and 869T/C polymorphisms could be used as genetic susceptibility markers of the NPC.

Interleukin-8 and CXCR1 Receptor Functional Polymorphisms and Susceptibility to Acute Pyelonephritis

We performed a case-control study in children diagnosed by the first episode of upper urinary tract infection with or without vesicoureteral reflux to evaluate the association of functional polymorphism of interleukin-8 (-251A>T and +2767A>G), and its receptor CXCR1 (+2607G>C). Genomic DNA was obtained from 265 children with a clinical and laboratory diagnosis of urinary tract infection who were recruited in northeast Italy. The children were subdivided as 173 who were dimercapto-succinic acid scan positive with positive static renal scintigraphy in acute conditions, consistent with the diagnosis of acute pyelonephritis, and 92 who were dimercapto-succinic acid scan negative. Genetic analysis for the same polymorphisms was also extended to a control population of 106 umbilical cord DNA samples. Statistical analysis of genotype data showed that 1) the tested populations were in Hardy-Weinberg equilibrium, 2) there were significant differences between the dimercapto-succinic acid scan positive and negative groups (p=0.049), and the dimercapto-succinic acid scan positive group vs controls (p=0.032) in terms of interleukin-8 -251A>T polymorphism frequency, 3) there was also a significant difference in the distribution of IL-8 -251A>T and +2767A>G polymorphisms between dimercapto-succinic acid scan positive and negative children in the subgroup without vesicoureteral reflux (p=0.03 and 0.02, respectively) and 4) no significant differences were found in the frequency of the distribution of CXCR1 +2607G>C polymorphism in all groups. These data suggest that the gene for the proinflammatory chemokine interleukin-8 is involved in susceptibility to acute pyelonephritis during upper urinary tract infection in children with or without vesicoureteral reflux.

Analysis of transforming growth factor-β1 gene polymorphisms in patients with Hepatitis C infection

Analysis of transforming growth factor-β1 gene polymorphisms in patients with Hepatitis C infection

The Relationship of Transforming Growth Factor-β1 Gene Polymorphism, Its Plasma Level, and Gingival Overgrowth in Renal Transplant Recipients Receiving Different Immunosuppressive Regimens.

Cyclosporin A (CsA) induces gingival overgrowth (GO) in patients who seem to be prone to this disorder. It is still impossible to determine which patients will develop GO. Patients treated with the new immunosuppressive drug tacrolimus seem not to have GO. The aims of this study were to investigate transforming growth factor-β1 (TGF-β1) gene polymorphisms in renal transplant recipients treated with CsA or tacrolimus and to establish an association between these polymorphisms and TGF-β1 plasma concentration and the incidence of GO. The examined group consisted of 134 renal transplant recipients. Ninety-two underwent CsA treatment (50 with and 42 without GO), and 42 underwent tacrolimus treatment. Age, gender, time after transplantation, calcineurin inhibitor total dosage, number of teeth, and sulcus bleeding index were analyzed. TGF-β1 plasma levels were estimated in 60 CsA- and 30 tacrolimus-treated patients. Two biallelic polymorphisms of the TGF-β1 gene were studied at codon 10 (at position +869) and at codon 25 (at position +915) in patients from the examined group and in 108 healthy volunteers (the control group). The distribution of the high, intermediate, and low TGF-β1 producer phenotypes was comparable in all the studied groups and in the healthy controls. The high producer phenotype was more frequent in patients with GO. TGF-β1 levels in the CsA group showed correlation with the phenotypes. The lowest incidence of GO was observed in the 10C/C genotype, whereas the highest was observed in the 10T/C genotype. High and intermediate TGF-β1 producer phenotypes and heterozygous genotype 10T/C might be considered risk factors for GO in patients treated with CsA.

ASSOCIATION OF TRANSFORMING GROWTH FACTOR-β1 GENE POLYMORPHISM WITH REFLUX NEPHROPATHY

Reflux nephropathy (RN) is recognized as a major cause of end stage renal failure in children and young adults. Transforming growth factor-beta1 (TGF-beta1) is a potent proinflammatory and fibrogenetic cytokine known to have a key role in the regulation of renal tissue fibrosis. We investigate genotype frequencies for polymorphisms of the TGF-beta1 gene at position -509, codon 10 and 25, and examine circulating levels of TGF-beta1 in patients with reflux nephropathy. Renal scaring was evaluated with 99technetium dimercapto-succinic acid renal scan. Genotyping was performed in 123 patients with severe to moderate reflux nephropathy and 58 controls for the position -509, the coding region at position 10 and 25 of the TGF-beta1 gene polymorphisms by polymerase chain reaction, gel analysis and appropriate restriction digest. TGF-beta1 serum levels were measured with standard ELISA technique. The genotype distribution of -509-CT was significantly increased in the RN group compared to controls, (82% vs 37%). Similarly, there was a significant increase in the CC Lue(10)-->Pro (codon 10) genotype (77% vs 27.5%, p <0.05), while TC Lue(10)-->Pro was significantly lower (7.3% vs 43%, p <0.05) in patients compared to controls. There was no significant difference in the Arg(25)-->Pro (codon 25) TGF-beta1 genotypes distribution between patients and controls. There were no statistically significant differences in the serum levels of TGF-beta1 in children with RN (4.2 +/- 0.3 mIU/ml) compared to controls (3.9 +/- 0.4 mIU/ml) (p >0.05). Patients with TGF-beta1 -509 and Lue(10)-->Pro gene polymorphisms may be at higher risk for reflux nephropathy.

Transforming growth factor-β1 gene polymorphisms associated with chronic obstructive pulmonary disease in Chinese population

To determine the frequencies of polymorphism and haplotype in the transforming growth factor-beta 1 (TGF-beta1) gene promoter in the Chinese population and to investigate the susceptibility of this population to chronic obstructive pulmonary disease (COPD). The target fragments of the TGF-beta1 gene promoter were amplified and analyzed by polymerase chain reaction-restriction fragment length polymorphism technique in 84 COPD patients and 97 age- and sex-matched healthy controls. The test for Hardy-Weinberg equilibrium was performed using HWE program of the LINKUTIL package and statistical analysis was carried out with the SPSS statistical package. An expectation maximization algorithm was used for the pairwise linkage disequilibrium test and haplotype analysis. More carriers of the -800A allele, or fewer carriers of the -509T allele, were detected in the COPD patients compared with the non-symptomatic control subjects [for the -800A allele, 29.8% vs 14.4%, respectively, Chi2=6.257, degrees of freedom (df)=1, P=0.012; for the -509T allele, 27.3% vs 44.3%, respectively, Chi2=5.582, df=1, P=0.018]. The prevalence of the -800A allele was significantly higher in the COPD patients than in control subjects (P=0.009), whereas the frequency of the -509T allele was significantly higher in control subjects than in the COPD patients (P=0.008). In addition, this distribution tendency for the -800A or -509T allele was similar in heavy smokers (smoking history >20 pack years); (number of packs of cigarettes per day multiplied by the number of years of smoking) Chi2=7.235, P=0.007, and Chi2=5.636, P=0.018, respectively). The linkage disequilibrium was found between -800 G-A and -509 C-T (D>0.60, P<0.0001), and the frequency of the AC haplotype, consisting of the least common base at -800 and the most common base at -509, was significantly higher in patients with COPD than in controls (0.056 vs 0.021, P<0.05). The single nucleotide polymorphism (SNP) in the TGF-beta1 gene promoter might be associated with COPD, and the -800A/-509C haplotype is possibly one of the susceptibility factors for COPD.

Colonic motility in the cat. IV. Peripheral pathways mediating the effects induced by hypothalamic and mesencephalic stimulation.

Rostad, H. Colonic motility in the cat. IV. Peripheral pathways mediating the effects induced by hypothalamic and mesencephalic stimulation. Acta physiol. scand. 1973. 89. 154–168. The peripheral pathways by which the hypothalamus and mesencephalon influence the motility of the colon have been studied by combining brain stimulation and peripheral nerve sectioning, and by use of autonomic blocking agents. Excitatory colonic effects induced from the hypothalamic sympatho-inhibitory area with concomitant blood pressure falls were found to be mediated through the sympathetic lumbar colonic nerves, whereas excitatory responses with associated blood pressure rises were conveyed through the latter as well as through the parasympathetic pelvic nerves. On the other hand, the augmentatory colonic effects usually associated with blood pressure rise evoked from the mesencephalon were conveyed through the lumbar colonic nerves only. The responses through the lumbar colonic and pelvic nerves were blocked by guanethidine and atropine, respectively. The augmentatory colonic responses from the hypothalamic sympatho-inhibitory area were blocked by the beta-adrenergic blocking agent propranolol, whereas the effects from the other responsive hypothalamic areas, transmitted through the lumbar colonic nerves, were blocked by alpha-blocker (phenoxybenzaminc), but not by propranolol. This finding support the presence of alpha-excitatory receptors in the colonic wall. Inhibition of colonic motility induced by hypothalamic and mesencephalic stimulation, weir found to be mediated through the lumbar colonic as well as through the splanchnic nerves. The effects were blocked by guanethidine, and those from the responsive hypothalamic zones were also blocked by propranolol.

Transforming growth factor-β1 gene polymorphisms are associated with progression of liver fibrosis in Caucasians with chronic hepatitis C infection

Considerable attention is focused on polymorphisms in the gene encoding transforming growth factor-beta1 (TGF-beta1), a multifunctional cytokine that is in turn a potent growth inhibitor involved in wound healing and differentiation. In humans, it promotes the pathogenesis of organ fibrosis, atherosclerosis, cancer, autoimmune and inflammatory diseases, keloid disease, and hypertrophic scarring. For this reason, much emphasis has been placed on studies elucidating the impact of TGF-beta1 and its gene variations for the susceptibility and pathogenesis of these diseases. Unfortunately, some studies have serious limitations. We have recently described a high-throughput method for investigation the Arg25Pro polymorphism of human TGF-beta1 gene and showed that the frequency of the Pro25 allele is significantly associated with hepatic fibrogenesis. In this report, we describe two novel LightCycler (LC) techniques that facilitate the examination of the two other known alterations in the coding region of TGF-beta1. We investigated whether these polymorphisms contribute to hepatitis-induced progression of fibrogenesis in Chinese and Caucasians. In the Chinese ancestry, the gene polymorphisms at codons 25 and 263 were not found and the genetic variant at codon 10 is unlikely to confer susceptibility to hepatic fibrosis. Contrarily, in Caucasians TGF-beta1 allelic variations are more frequent and the presence of prolines either in codon 25 or 10 is associated with the interindividual variability in developing more severe fibrosis during chronic hepatitis C infection. In summary, these results confirm the hypothesis that TGF-beta1 polymorphisms are associated with fibrosis progression in Caucasians chronically infected with hepatitis C.

Transforming growth factor-β1 gene polymorphism in renal transplant recipients

Transforming growth factor-β1 gene polymorphism in renal transplant recipients

The transforming growth factor-β1 gene polymorphism (G915C) is not associated with systemic lupus erythematosus

Lymphocyte production of transforming growth factor (TGF)-beta1 is decreased in systemic lupus erythematosus (SLE). The lack of this immunoregulatory cytokine may contribute to the characteristic T cell disregulation and aberrant B cell stimulation in SLE patients. The less common C allele of the TGFB1 polymorphism (G915C) is associated with a lower TGF-beta1 production capacity. We performed a population-based case-control study to analyse the impact of this polymorphism on disease susceptibility, on clinical SLE manifestations and autoantibody production. A total of 203 German Caucasian SLE patients (fulfilling the 1982 ACR disease duration 11.5 +/- 7.0 years) and 158 ethnically, age- and sex-matched healthy controls were genotyped with a mutagenically separated polymerase chain reaction. There were no significant differences in the genotype distribution and allele frequencies between patients (915 C = 0.08) and healthy controls (915 C = 0.10). Comparing subgroups of patients, we found no association of major disease manifestations or specific autoantibodies with TGFB1 genotypes or alleles. The TGFB1 polymorphism (G915C) neither significantly contributes to the disease susceptibility, nor predisposes to clinical and immunological manifestations typical of SLE. Further studies are needed to corroborate the pathogenic role of TGF-beta1 in SLE patients and to identify the precise genetic elements controlling its production.

Transforming growth factor-beta1 gene polymorphisms and coronary artery disease.

1. Transforming growth factor-beta1 is a cytokine with a very wide spectrum of biological activities. Previous studies have shown that it is involved in a number of physiological and pathological processes including heart disease. In our study we aimed to scan the transforming growth factor-beta1 locus for polymorphisms and to identify haplotypes significantly associated with a predisposition to coronary atherosclerosis.2. Two patient groups comprising 244 angiographically normal individuals and 655 patients with coronary artery disease were recruited from London and Sheffield. DNA samples from these subjects were screened for mutations in the transforming growth factor-beta1 locus and all subjects were genotyped by a coupled polymerase chain reaction-restriction enzyme digestion method.3. Five polymorphisms have been identified in the transforming growth factor-beta1 gene at positions G-800A, C-509T in the promoter region, Leu10-->Pro, Arg25-->Pro in exon 1 and Thr263-->Ile in exon 5. No significant difference in frequencies for any of the five polymorphisms was found between controls and patients with coronary artery disease. Similarly, there was no correlation between these polymorphisms and hypertension.4. The genotypes of all the individuals participating in the study were assigned to seven main haplotypes of the transforming growth factor-beta1 locus. Based on species comparison data we propose that GCCGC is the ancestral haplotype in humans.5. Our data suggest that these transforming growth factor-beta1 polymorphisms are not associated with coronary artery disease and therefore their presence alone would not be a genetic risk factor for predisposition to coronary artery disease.