Polymerase Chain Reaction-based Restriction Analysis Research Articles

LOX-1 gene variants and maternal levels of plasma oxidized LDL and malondialdehyde in patients with gestational diabetes mellitus.

The aim of this study was to investigate the relationships between the maternal levels of oxidized LDL (ox-LDL), lipid peroxidation marker malondialdehyde (MDA) and LOX-1 3'UTR188C/T and K167N single nucleotide polymorphisms in pregnant Turkish women with gestational diabetes mellitus (GDM). 116 pregnant women with GDM and 120 healthy pregnant women from the same geographic region were included in the study. Polymerase chain reaction-based restriction analysis was used to identify 3'UTR188C/T and K167N polymorphisms of the LOX-1 gene. Plasma ox-LDL and MDA levels were determined by enzyme-linked immunosorbent assay and spectrophotometric method in all study subjects, respectively. Our results indicated that the distribution of the LOX-1 3'UTR188C/T and K167N genotypes and alleles did not differ significantly among subjects with or without GDM (p > 0.05). TT and NN genotype carriers are associated with some glucose metabolism parameters (p < 0.05). There were no significant differences among plasma ox-LDL and MDA levels with regard to LOX-1 3'UTR188C/T and K167N polymorphisms in GDM group and control subjects (p > 0.05). According to the combined genotype analysis of LOX-1 3'UTR 188 TT and K167N NN polymorphisms, plasma MDA and ox-LDL levels were significantly different between women with GDM and healthy subjects either with or without combined TT/NN genotype carriers (p < 0.001). According to our results, ox-LDL and MDA levels were increased in GDM pregnant women and healthy pregnant women either with or without combined TT/NN genotype carriers, for our Turkish sample, these genotype carriers appear to be related with increased oxidative stress in patients with GDM.

The rs42524 COL1A2 polymorphism is associated with primary intracerebral hemorrhage in a Chinese population

Hypertensive arteriosclerosis and amyloid angiopathy account for 78–88% of primary cerebral hemorrhages, and collagen plays a critical role in the pathology of these hemorrhages. The COL1A2 gene on chromosome 7q22.1 has been shown to be associated with intracranial aneurysms. In our study, 393 Han Chinese patients with primary intracerebral hemorrhage (mean age 58.49±9.49years) and 486 controls (mean age 59.22±8.79years) underwent genotyping for the rs42524 polymorphism of COL1A2 using polymerase chain reaction-based restriction analysis. Differences in genotypic and allelic frequencies between the cases and controls were evaluated using the χ2 test. The association between the rs42524 polymorphism and primary intracerebral hemorrhage was also tested using logistic regression analysis with adjustment for risk factors. We found that there was a significant difference between patients with primary intracerebral hemorrhage and control subjects with respect to genotype distribution (χ2=16.33, P<0.001) and allelic frequencies (χ2=15.01; P<0.001; odds ratio 2.261; 95% confidence interval 1.482–3.451) for the rs42524 polymorphism of COL1A2. Adjustment for risk factors did not change our conclusions. We conclude that the COL1A2 rs42524 polymorphism could be a genetic risk factor for primary intracerebral hemorrhage among Han Chinese.

Association of vitamin D receptor gene polymorphism and calcium urolithiasis in the Chinese Han population

To investigate the effect of the vitamin D receptor (VDR) Fok I Bsm I Dde I Apa I Taq I polymorphism on the clinical presentation of calcium urolithiasis, 464 patients with urolithiasis and 450 age- and sex-matched healthy controls were recruited from The First Affiliated Hospital of Zhejiang University between January 2010 and March 2011. Five SNPs of VDR polymorphism were detected using polymerase chain reaction-based restriction analysis. The frequency of VDR Apa I genotypes between the patients and the healthy controls was significantly different (P = 0.006). Apa I a allele was found to be associated with increased risk of stone recurrence (P = 0.028). We also found Fok I Dde I Apa I showed a significant difference between male and female in the patients group (P < 0.05). Haplotype analysis of the five VDR polymorphisms showed a significant association with urolithiasis (global-P value = 0.0001). Genetic polymorphisms of VDR are important in the clinical presentation of patients with calcium urolithiasis in the Han population of southern China.

Fibrillin-1 gene intron 56 polymorphism in Turkish children with mitral valve prolapse

Mitral valvar prolapse is the most common anomaly of the mitral valve apparatus throughout childhood. Fibrillin is one of the structural components of the elastin-associated microfibrils found in the mitral valve. A case-controlled study has performed to investigate the relationship between fibrillin 1 gene intron 56 polymorphism and risk of mitral valvar prolapse in Turkish children. A total of 77 patients with mitral valvar prolapse diagnosed by clinical evaluation and echocardiography and 89 normal children of same age and sex were studied. The fibrillin-1 gene intron 56 polymorphism was identified by the polymerase chain reaction-based restriction analysis. There was a significant difference in the distribution of fibrillin-1 gene intron 56 genotypes (p = 0.0001) and allelic frequency (p = 0.0001) between the cases and the controls. Patients with mitral valvar prolapse have higher frequencies of fibrillin-1 gene intron 56 GC genotypes. Healthy children have higher frequencies of fibrillin-1 gene intron 56 CC genotypes. We speculate that the higher frequency of fibrillin-1 gene intron 56 G-allele increases the risk of mitral valvar prolapse.

The Ala Allele at Val762Ala Polymorphism in Poly(ADP-ribose) Polymerase-1 (PARP-1) Gene is Associated with a Decreased Risk of Asthma in a Turkish Population

Background and objective. It has been suggested that inhibition of poly (ADP-ribose) polymerase-1 (PARP-1), either pharmacologically or by a gene knockout provides significant protection against systemic or tissue inflammation in animal models. The aim of this study was to analyze the association of the PARP-1 Val762Ala polymorphism, which has beenreported to be associated with decreased enzymatic activity, in Turkish patients with adult asthma. Methods. A total of 112 subjects with stable asthma and 180 normal controls from the same geographic region were studied and polymerase chain reaction-based restriction analysis was used to identify Val762Ala polymorphism of the PARP-1. Results. In univariate analysis, PARP-1 762 AA genotype conferred a 3.4 fold reduction in risk (OR = 0.297, 95% CI = 0.105-0.813; P = 0.014), while heterozygous VA genotype conferred an even greater level of protection (OR = 0.06; 95%CI, 0.026-0.14; P < 10−6). In addition, wild type PARP-1 762 V allele had 5 times the risk of developing asthma than those without the allele (OR 0.199, CI 0.118-0.334, P = 10−6). Conclusions. These findings suggest that PARP-1 V762A variants may be one of the factors participating in protection or susceptibility to asthma in our population.

Polymorphism rs42524 of COL1A2 and sporadic intracranial aneurysms in the Chinese population

The COL1A2 gene at 7q22.1 has been shown to be associated with familial intracranial aneurysms (IAs) in the Japanese population. In the present study, the authors investigated the correlation between the presence of the rs42524 polymorphism in COL1A2 and the occurrence of sporadic IAs in Chinese patients. The polymorphism rs42524 of the COL1A2 gene was identified by polymerase chain reaction-based restriction analysis in genomic DNA from 226 patients with sporadic IAs (mean age 51.49 +/- 11.47 years) and 326 control participants (mean age 52.33 +/- 10.50 years). Neurological assessments were performed using the Hunt and Hess grading system, and differences in allelic and genotypic frequencies between the patient and control groups were evaluated with the chi-square test. There was a significant difference in either the genotype distribution (chi(2) = 11.99, p = 0.002) or allelic frequencies (chi(2) = 11.96, p = 0.001, odds ratio 2.579, 95% confidence interval 1.486-4.476) between patients with IAs and patients in the control group. The rs42524 polymorphism of COL1A2 could be a genetic risk factor for sporadic IAs among individuals of Chinese Han ethnicity. This study is the first to confirm the association between COL1A2 and IAs.

Association of leptin −2548G/A and leptin receptor Q223R polymorphisms with increased risk for oral cancer

We investigated the possible association of DNA polymorphisms -2548G/A and Q223R in the leptin (LEP) and leptin receptor (LEPR) genes, respectively, which both affect the amount of circulating cytokine-type hormone leptin, with risk for development of oral cancer. Polymerase chain reaction-based restriction analysis was performed in DNA samples of 150 patients with oral squamous cell carcinoma (OSCC) and 152 healthy control subjects of equivalent gender, age, and ethnicity (Greeks and Germans). Compared to controls, the homozygous high gene expression genotype A/A of the LEP -2548G/A polymorphism was significantly increased in the subgroups of patients with advanced cancer stages (P = 0.0001; OR 9.0, 95% CI 2.62-30.89), with a positive family history of cancer (P = 0.0346; OR 3.55, 95% CI 1.15-11.01), without tobacco abuse (P = 0.0051; OR 9.69, 95% CI 1.03-91.24), and without alcohol abuse (P = 0.0472; OR 2.16, 95% CI 0.87-5.37). The homozygous low-leptin-binding genotype G/G of the LEPR Q223R polymorphism was strongly associated with an increased risk for OSCC for all patients (P = 0.0028; OR 4.11, 95% CI 1.30-12.97) as well for most of the patient subgroups. The above findings are consistent with the growth-promoting role of leptin in cancer and its induction effect on angiogenesis and metastasis. This is the first study indicating the association of these LEP and LEPR gene polymorphisms with increased risk for OSCC.

Association of urokinase gene 3′-UTR T/C polymorphism with calcium oxalate urolithiasis in children

Urokinase is synthesized by various cells such as kidney, pneumocytes, and phagocytes. It cleaves plasminogen to plasmin and hence stimulates fibrinolysis. Urokinase breaks down the matrix protein within the stone and thus prevents stone formation and growth. Urokinase concentrations are lower and urokinase gene 3'-UTR T/C polymorphism is higher in patients with recurrent stones. Our aim was to investigate the role of urokinase gene 3'-UTR T/C polymorphism in childhood recurrent stone disease. A control group of 40 healthy children having no history of stone formation (group 1) (mean age 10.5+/-4.2 years), 40 children (mean age 10.5+/-4.33 years) who had calcium oxalate stones for the first time (group 2), and 40 patients (mean age 11.2+/-3.8 years) with recurrent calcium oxalate stone disease (group 3) were included in the study. The groups were compared with respect to age, gender and urokinase gene 3'-UTR T/C polymorphism. Polymerase chain reaction-based restriction analysis was used to identify C/T polymorphism of the urokinase gene. No significant difference was observed between the three groups with respect to age and gender, while urokinase gene 3'-UTR T/C gene polymorphism was observed in four patients (10%) from group 3. In groups 1 and 2 there was no patient with T/C polymorphism. Urokinase 3'-UTR T/C gene polymorphism seems to appear more commonly in children with recurrent calcium oxalate stone disease than in healthy children and in those with stones for the first time. These results suggest that the urokinase gene might play a role in childhood recurrent calcium oxalate stone disease.

Association of Interleukin-1βGene and Receptor Antagonist Polymorphisms with Calcium Oxalate Urolithiasis

Genetic polymorphisms of the interleukin-1beta (IL-1beta) promoter region (-511) and exon 5 +3954 and a variable number of tandem repeats in the IL receptor antagonist (IL-1RA) gene have been proposed as markers for calcium oxalate urolithiasis. Because the prevalence of these polymorphisms could be influenced by racial variation/ethnicity, we explored the association of IL-1 gene-cluster polymorphisms with stone formation in a north India population. The case-control study involved 150 stone-free control subjects (mean age 46.5 +/- 10.5 years) and 130 patients (mean age 40.0 +/- 11.5 years) with calcium oxalate urolithiasis. Biallelic polymorphisms of two loci, IL-1beta (-511) and IL-1beta (+3954), as well as the penta-allelic variable number of tandem repeats of IL-1RA, were genotyped by polymerase chain reaction-based restriction analysis. Haplotypes were constructed for the IL-1 gene cluster using SNP Analyzer software. We observed a significant association between stone disease and IL-1beta -511 and IL-1RA polymorphisms (P < 0.001 and P = 0.039, respectively), whereas no association was observed for IL-1beta +3954 (P = 0.408). The frequency of the TT (-511) and I/II (410/240; IL-1RA) genotypes was higher in patients than in control subjects (50/130 v 16/150 and 55/130 v 38/150, respectively), whereas the frequencies of the haplotypes were similar (P = 0.485). Significant linkage disequilibrium showed that three genes were strongly linked (P < 0.0001). Patients with a combination of high IL-1beta (-511 and +3954) and low IL-1RA genotypes were at significantly higher risk for urolithiasis (P < 0.001; odds ratio = 5.448, 0.013, and 2.560, respectively). Our study demonstrated a strong association of IL-1RA and IL-1beta-511 and suggested that differences in the IL-1 gene cluster could be linked to the risk of urolithiasis. A combination of IL-1beta and IL-1RA associations exhibiting gene-gene interaction further substantiates the finding of risk.

Interleukin-1β Exon 5 and Interleukin-1 Receptor Antagonist in Children With Immune Thrombocytopenic Purpura

Immune thrombocytopenic purpura (ITP) is associated with cytokine response and dysregulation of the cytokine network. We investigated the polymorphisms of interleukin (IL)-1beta exon 5 and IL-1 receptor antagonist (IL-1 Ra) in 50 children with acute ITP, in 30 children with chronic ITP, and in 100 healthy children by polymerase chain reaction-based restriction analysis. No significant differences in either genotype distribution (P=0.52) or allelic frequencies (P=0.70) were found among children with acute ITP, chronic ITP, or controls for IL-1beta exon 5. However, significant differences in genotype distribution (P=0.02) and the allelic frequencies (P=0.007) were found among children with acute ITP, chronic ITP, and controls for IL-1 Ra. We found that the IL-1 Ra but not IL-1beta gene polymorphism was associated with childhood ITP. This finding suggests that the IL-1 Ra gene polymorphism is implicated in the pathophysiology of childhood ITP.

AGT and ACE genes influence classic mitral valve prolapse predisposition in Marfan patients

Background In Marfan syndrome, the mitral valve prolapse, ranging from nonclassic to classic form on the basis of the leaflet thickness, is a common condition characterized by a highly variable structural abnormality. We investigated the role of angiotensinogen ( AGT) M235T, angiotensin converting enzyme ( ACE) I/D and angiotensin II type 1 receptor ( AT1R) A1166C polymorphisms in influencing the susceptibility to classic or non-classic mitral valve prolapse in Marfan patients. Methods We studied 135 Marfan patients with mitral valve prolapse, diagnosed by echocardiography. AGT, ACE, and AT1R polymorphisms were identified by polymerase chain reaction-based restriction analysis. Results The frequency of the ACE D, but not AGT 235T and AT1R 1166C allele, was significantly higher in patients with classic mitral valve prolapse in comparison to that observed in the non-classic one ( p = 0.03). The percentage of subjects with the contemporaneous presence of ACE D and AGT 235T alleles was significantly higher in the classic mitral valve prolapse group in comparison to the non-classic one (79% vs. 55%, respectively; p = 0.008). The concomitant presence of these two alleles was associated with increased susceptibility to the classic mitral valve prolapse ( OR 3.02, p = 0.016). Conclusions Our findings show a possible role of ACE and AGT genes as predisposing factors to classic mitral valve prolapse in Marfan patients, thus suggesting a role of renin angiotensin system genes in modulating mitral valve abnormality, and the need for an interventional study with angiotensin II type 1 receptor antagonists, which considers the leaflet thickness progression in Marfan patients with MVP.

Tumor Necrosis Factor-α Gene G-308A and G-238A Polymorphisms are Not Associated with Rheumatic Heart Disease in Taiwan

Purpose. The aim of this study was to test whether tumor necrosis factor (TNF)-α gene polymorphisms could be used as markers of susceptibility or severity of rheumatic heart disease (RHD) among the Chinese population in Taiwan. Methods. A group of 115 patients with RHD diagnosed by echocardiography, and another group of 103 age and sex-matched normal control subjects were studied. TNF-α gene G-308A and G-238A polymorphisms were identified by polymerase chain reaction-based restriction analysis. Results. There was no significant difference in the distribution of genotypes and allelic frequencies of the TNF-α gene G-308A and G-238A polymorphisms between RHD patients and controls. Further categorization of RHD patients into mitral valve disease and combined valve disease subgroups also revealed no statistical difference in these gene polymorphisms when compared with controls. Conclusions. These findings suggest that the TNF-α gene G-308A and G-238A polymorphisms are not suitable genetic markers for RHD in Taiwan Chinese.

E-Cadherin Gene 3′-UTR C/T Polymorphism Is Associated with Prostate Cancer

Introduction: E-cadherin (CDH-1) is a cell-cell adhesive molecule which maintains cell integrity and communication between the intracellular and extracellular world. CDH-1 may therefore be related to carcinogenesis. A polymorphism located at the 3′-UTR of the CDH-1 gene is associated with stone disease; however, its relationship to prostate cancer has not been reported. We aimed to study whether there is an association between the 3′-UTR polymorphism and prostate cancer. Materials and Methods: We collected 96 patients with prostate cancer and 114 normal controls for this study. The polymorphism of the CDH-1 gene was studied by polymerase chain reaction-based restriction analysis. Results:There was a significant difference in genotype distribution of the CDH-1 gene polymorphism between cancer patients and normal controls (p < 0.001). The distribution of the CDH-1 gene CC genotype in prostate cancer patients (51.0%) was higher than in the controls (10.5%). The odds ratio for the CDH-1 ‘C’ allele was 2.896 (95% CI = 1.908–4.396). There was no significant difference according to age, pathological grading, clinical staging, and responsiveness to hormonal therapy among patients. Only 3 patients (3.1%) had a history of urolithiasis. Conclusions:The CDH-1 gene 3′-UTR C/T polymorphism is associated with prostate cancer. The ‘CC’ homozygote indicates a relatively higher risk for developing prostate cancer than other genotypes.

TAP 2 Gene Msp-I Polymorphism Might Be Associated with Calcium Oxalate Stone Disease

Introduction: Inflammation might be one of the causes of stone disease. The function of the transporter associated with antigen-processing protein (TAP) is related to immune response and inflammation. Our aim was to investigate the relationship between stone disease and 5 polymorphic sites of the TAP gene (TAP1-1, 1-2, 2-1, 2-2, 2–3). Materials and Methods: We compared the frequencies of 5 polymorphisms in the TAP gene between 208 patients with recurrent calcium oxalate stone and 210 healthy controls. The polymorphism was detected by polymerase chain reaction-based restriction analysis. Results: Significant differences in the frequency of the polymorphism at the TAP2-2 site were detected between normal individuals and calcium stone disease patients (p < 0.0001). The distribution of the genotype AA homozygote was higher in stone patients (33.3%) than in the control group (16.3%). The odds ratio for the A allele compared with the G allele was 2.097 (95% CI 1.571–2.802). Conclusions: We conclude that the TAP2-2 MspI polymorphism might be associated with calcium stone disease.

Vascular endothelial growth factor gene-460 C/T polymorphism is a biomarker for oral cancer

Oral cancer is one of the most common malignant diseases in Taiwan. The incidence of male oral cancer is 9.01 times than that of female. The formation or progression of oral cancer may be associated with a polymorphism of the vascular endothelial growth factor (VEGF) gene. The most frequently seen polymorphism is BstUI (C to T) located at the -460th nucleotide upstream of the VEGF gene. We investigated whether this polymorphism could be a genetic marker of oral cancer. A normal control group of 230 healthy people and 137 patients with oral cancer were examined. The polymorphism was detected by polymerase chain reaction-based restriction analysis. The analysis revealed significant differences between normal individuals and patients with cancer (P<0.001). The distribution of the "TT" homozygote in the patient group was greater than that in the control group. The odds ratio per copy of the "T/C" ratio was 9.62 (95% confidence interval 5.81-15.87), which means that for a group of people with a higher T/C ratio have higher risk in getting oral cancer. There is no gender difference in this VEGF gene polymorphism. Therefore, the BstUI polymorphism of the VEGF gene is a suitable genetic marker of oral cancer.

Interleukin‐4 gene intron‐3 polymorphism is associated with transitional cell carcinoma of the urinary bladder

To evaluate whether polymorphism of the interleukin-4 gene exon 3, and of the interleukin-1beta gene exon 5 and promoter region, are associated with transitional cell carcinoma (TCC) of the urinary bladder, as cytokines are hypothesized to be important in cancer formation. The study included 138 patients with TCC of urinary bladder and 105 healthy controls living in the same area. Each genetic polymorphism was typed using polymerase chain reaction-based restriction analysis. Genotype distribution and allelic frequencies between patients and controls were compared. There were significant differences in genotype and allelic distribution of intron 3 RP1/RP2 polymorphism (P < 0.001), but no significant difference in genotype distribution or allelic frequencies of the interleukin-1beta gene polymorphism between patients with bladder cancer and controls. The interleukin-4 gene intron 3 polymorphism is associated with bladder cancer and is a potential genetic marker in screening for the possible causes of bladder cancer.

CYP17 and tumor necrosis factor-α gene polymorphisms are associated with risk of oral cancer in Chinese patients in Taiwan

ConclusionPatients who carry the T/T homozygote of CYP17 C/T gene polymorphism may have a higher risk of developing oral cancer.ObjectiveCancer of the oral cavity is the most commonly seen malignancy in Taiwan, and its rising incidence poses a formidable challenge to oncologists. The CYP17 gene encodes P450c17alpha, an enzyme involved in the metabolism of steroid hormones. Tumor necrosis factor-α (TNF-α) is one of the cytokines produced by macrophages, and its function has been postulated to play a role in cancer formation. We investigated whether polymorphisms of CYP17 and TNF-α genes are associated with oral cancer.Material and methodsPolymorphisms of CYP17 and TNF-α genes were detected by polymerase chain reaction-based restriction analysis in 137 patients with oral cancer and 102 normal controls.ResultsThe results for the CYP17 gene revealed a significant difference between oral cancer patients and normal controls (p=0.0063), but there was no significant difference for the TNF-α gene (p=0.4753).

Lack of Association of Genetic Polymorphisms in the Interleukin-1 .BETA., Interleukin-1 Receptor Antagonist, Interleukin-4, and Interleukin-10 Genes With Risk of Rheumatic Heart Disease in Taiwan Chinese

Inflammation and genetics may play a role in the pathogenesis of rheumatic heart disease (RHD). The aim of this study was to test whether interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1Ra), IL-4, or IL-10 gene polymorphisms could be used as markers of susceptibility to or severity of RHD among the Chinese population in Taiwan. A group of 115 patients with RHD diagnosed by echocardiography, and 163 age- and sex-matched normal control subjects were studied. IL-1beta promoter, IL-1beta exon 5, IL-1Ra, IL-4 promoter, IL-4 intron 3, and IL-10 gene polymorphisms were identified by polymerase chain reaction-based restriction analysis. There was no significant difference in the distribution of genotypes and allelic frequencies between RHD cases and controls for IL-1beta promoter, IL-1beta exon 5, IL-1Ra, IL-4 promoter, IL-4 intron 3, and IL-10 gene polymorphisms. Further categorization of the RHD patients into mitral valve disease and combined valve disease subgroups also revealed no statistical difference in these gene polymorphisms when compared with controls. These findings suggest that the IL-1beta, IL-1Ra, IL-4, or IL-10 gene polymorphisms are not suitable genetic markers for RHD in Taiwan Chinese.

Association of Vitamin D Receptor-Gene (FokI) Polymorphism with Calcium Oxalate Nephrolithiasis

Formation of kidney stones is still not understood but is hypothesized to be associated with the vitamin D receptor gene (VDR). In order to assess the eventual role of VDR start-codon FokI polymorphism in stone formation, we evaluated the association between calcium stone disease and this polymorphism in a North Indian population. A control group comprised of 166 healthy individuals (age range 22-58 years) and a group of 138 patients with calcium oxalate stones (age range 21-72 years) were examined. The polymorphism was detected using polymerase chain reaction-based restriction analysis. An unexcisable length of 265 bp (CC) and two fragments of 169 bp and 96 bp (TT) were obtained by FokI restriction digestion. There was a statistically significant difference between the control and patient groups (X2 test, P<0.001) for the genotype of the VDR FokI start-codon polymorphism. The odds ratio (with 95% CI) for the C allele in those at risk of stone disease was 1.654 (1.041, 2.628). The VDR frequency distribution was also statistically significant (P<0.001) in case of male sex. The frequency distribution for this genetic polymorphism was not statistically different in normocalciuric and hypercalciuric stone patients (P=0.355). The VDR FokI polymorphism may be a good candidate for a marker for calcium oxalate-stone disease. These findings may contribute a small piece to the understanding of the pathogenesis of urinary calculi.

Association between transforming growth factor-β1 gene C-509T and T869C polymorphisms and rheumatic heart disease

Background Scarring and collagen deposition in the valves and destruction of myocytes may result from the combined effects of a smoldering rheumatic process and a constant trauma to the mitral vlave or aortic valve by the turbulent flow in rheumatic heart disease (RHD). Transforming growth factor-β1 (TGF-β1) may be responsible for the increased valvular fibrosis and calcification in the pathogenesis of RHD. However, the role of TGF-β1 genetic variant in RHD has not been studied. This case-controlled study was carried out to investigate the possible relationship between the TGF-β1 gene C-509T and T869C polymorphisms and RHD among the Chinese population in Taiwan. Methods A group of 115 patients with RHD documented by using echocardiography and 100 age- and sex-matched healthy control patients were studied. TGF-β1 gene C-509T and T869C polymorphisms were identified with polymerase chain reaction-based restriction analysis. Results A significant difference was seen in the distribution of genotypes between patients with RHD and control patients for either TGF-β1 C-509T polymorphism ( P <.0001) or T869C polymorphism ( P <.0001). The frequency of TGF-β1 C-509T CC genotype was lower in the RHD group than in the control group (χ 2 = 19.05, P <.0001), which suggests that this genotype may confer protective effects against RHD. A significant difference was seen in the distribution of allelic frequency between patients with RHD and control patients for TGF-β1 T869C polymorphism ( P = .04). The odds ratio (OR) for risk of RHD associated with TGF-β1 T869C T allele was 1.49 (95% CI, 1.02–2.19). Further categorization of patients with RHD into mitral valve disease and combined valve disease subgroups revealed no statistical difference in these gene polymorphisms when compared with the 2 subgroups. Conclusions Patients with RHD have a lower frequency of TGF-β1 C-509T CC genotype and a higher frequency of T869C T allele, which supports a role for the TGF-β1 gene C-509T and T869C polymorphisms in determining the risk/protection of RHD in Taiwan Chinese patients.