Association between C-589T polymorphisms of interleukin-4 gene promoter and asthma: a meta-analysis

BACKGROUND: A number of studies of genetic epidemiology have assessed the association of C-589T (also referred to as C-590T; rs number, 2243250) polymorphisms in the promoter region of interleukin-4 (IL-4) gene with asthma in different populations. However, the results are inconsistent and inconclusive. OBJECTIVES: We performed a meta-analysis of the association between C-589T polymorphisms of IL-4 and asthma with the following objectives: to estimate the magnitude of the gene effect and the possible mode of inheritance. METHODS: A genetic model-free approach was used to perform a meta-analysis. Asthma (atopy status nondefined), nonatopic and atopic asthma subgroups were separately analyzed. Heterogeneity and publication bias were also explored. RESULTS: Our meta-analysis summarized the evidence regarding the association between C-589T polymorphisms in the promoter region of IL-4 gene and asthma. When all asthma groups were pooled, a significant association of increased asthma risk and T allele was found. In subgroup analysis, our results indicated a significant association and a recessive genetic mode of C-589T polymorphisms of IL-4 with atopic asthma. The CC genotype was about 21 percent less likely to have atopic asthma than the genotype CT and TT. However, C-589T polymorphisms were not significantly associated with nonatopic asthma. CONCLUSIONS: This meta-analysis suggests there may be an important effect of single nucleotide polymorphisms (SNPs) in the promoter region of IL-4 gene on the pathogenesis of atopic asthma. This warrants further investigation in larger studies and meta-analysis.     

白细胞介素2基因-330T/G和白细胞介素6基因-174G/C多态性与结核病易感性的Meta分析

目的 分析白细胞介素2(IL-2)基因-330T/G和IL-6基因-174G/C多态性与结核病易感性的关系。方法 在Medline、PubMed、EMBase、Web of Science、Elsevier Science Direct、万方数据库、中国知网(CNKI)和维普数据库中检索从1990年1月至2017年6月公开发表的关于IL-2和IL-6基因多态性与结核病易感性关系的中文和英文文献。初筛获得相关文献573篇,根据文献纳入和排除标准最终纳入文献12篇。应用Stata 12.0软件对各研究原始数据进行Meta分析。结果 IL-2基因-330T/G位点研究纳入文献共8篇,病例组971例,对照组1519名。Meta分析结果显示,欧洲人群中携带IL-2基因-330T等位基因者较携带-330G等位基因者患结核病风险低45%(T对G:OR=0.55;95%CI=0.31~0.98;P=0.042)。IL-6基因-174G/C位点纳入研究共9篇,病例组1445例,对照组1955名。Meta分析结果显示,美洲人群中携带IL-6基因-174G等位基因者患结核病风险是携带-174C等位基因者的1.65倍(G对C:OR=1.65;95%CI=1.28~2.13;P<0.01);亚洲人群中携带IL-6基因-174G等位基因者患结核病风险是携带-174C等位基因者的1.4倍(G对C:OR=1.40;95%CI=1.13~1.72;P=0.002)。结论 IL-2基因-330T/G位点等位基因T可能与欧洲人群结核病易感性风险降低相关;IL-6基因-174G/C位点等位基因G可能与美国人群和亚洲人群结核病易感性风险增加相关。     

Association of TNFA(-308G/A), IFNG(+874 A/T) and IL-10(-819 C/T) polymorphisms with protection and susceptibility to dengue in Brazilian population

Objective: To evaluate gene polymorphisms and their association with susceptibility to dengue.Methods: A retrospective case-control study was performed with 262 subjects,comprising 78 dengue fever(DF) patients, 49 dengue hemorrhagic fever(DHF) patients and 135 healthy controls. Genotypic and allelic profiles were identified using polymerase chain reaction based in real time and amplification-refractory mutation system.Results: We observed a protective association of IL-10(-819 C/T) C allele(P = 0.028,OR = 0.56, CI = 0.34–0.91) against DHF, while the C/T(P = 0.047, OR = 2.10,CI = 1.01–4.38) and T/T(P = 0.008, OR = 3.82, CI = 1.38–10.59) genotypes were associated with DHF and DF, respectively. The dominant model TNFA-308 GA + AA(P = 0.043, OR = 0.45, CI = 0.20–1.00) genotypes were found to have protective effect against dengue infection. A protective association among the IFNG(+874 A/T) A/T genotype against DF(P = 0.02, OR = 0.46, CI = 0.24–0.89) and DHF(P = 0.034,OR = 0.43, CI = 0.19–0.95) was observed. When the studied single-nucleotide polymorphism was analyzed in combination, the combination GTA(P = 0.022, OR = 2.95,CI = 1.18–7.41) was statistically significantly associated with susceptibility to DF and the combination GCT(P = 0.035, OR = 0.28, CI = 0.08–0.90) with protection against the development of DHF.Conclusions: This research identifies the association of the IFNG(+874 A/T), TNFA(-308 G/A), IL-10(-819 C/T) genotypes as a factor for protection, susceptibility and severity to dengue.     

Association between the polymorphisms of IL-4 gene promoter (-590C>T), IL-13 coding region (R130Q) and IL-16 gene promoter (-295T>C) and allergic asthma

Allergic asthma is a multifactorial disease, influenced by genetic and environmental factors. Recent family-based studies have revealed evidence for linkage of human chromosomes 5q31-33, 12q15-24, 11q13 and 15q23.6 as regions likely to contain genes related to asthma. Among the candidate genes in these regions are the genes encoding for human interleukin-4, interleukin-13 and interleukin-16. To evaluate this linkage, we examined an Iranian population of patients with asthma. A total of 30 patients with allergic asthma and 50 normal subjects were studied. Allergic asthma was confirmed using skin prick test and spirometry. DNA was extracted from blood cells and IL-4 (-590C>T), IL-13 (R130Q) and IL-16 (-295T>C) polymorphisms were determined by PCR-RFLP method. Out of 30 patients with allergic asthma, the following genotypes for IL-4, IL-13 and IL-16 cytokines were found: IL-4 genotypes consisted of 17 (56.7%) CC, 8 (26.7%) CT and 5 (16.7%) TT; IL-13 genotypes consisted of 11 (36.7%) GG, 13 (43.3%) GA and 6 (20%) AA; IL-16 genotypes consisted of 23 (76.7%) TT and 7 (23.3%) CT. No patient showed CC genotype for IL-16. A higher proportion of case subjects with the C allele for the IL-4, G allele for the IL-13 and T allele for the IL-16 polymorphisms was found compared with the T, A and C alleles, respectively. These results suggest an influence of genetic variability at the promoter of IL-4 gene (-590C>T) and a coding region of IL-13 gene (R130Q) on the occurrence of allergic asthma and no relationship between IL-16 promoter polymorphism (-295T>C) and this disease.     

Association of interleukin-10 promoter single nucleotide polymorphisms -819 T/C and -592 A/C with aging

Increased inflammatory activity is known to accompany aging. Single nucleotide polymorphisms of inflammatory mediator genes might therefore affect the aging process. Relation of eight SNPs (tumor necrosis factor-alpha [TNF-alpha] -1031 T/C, interleukin-10 [IL-10] -819 T/C, IL-1beta -511 C/T, IL-6 -634 C/G, IL-18 -607 A/C, transforming growth factor-beta [TGF-beta] +869 C/T, matrix metalloproteinase-1 [MMP-1] -1607 1G/2G, and MMP-3 -1171 5A/6A) with age or gender was evaluated in 500 Japanese persons (mean age: 56.7 years old, range: 19-100) by the chi-square test. There was a significant association of IL-10 -819 T/C with age (p =.0026). The association remained significant after multivariate logistic regression analysis (odds ratio for an age interval for 1 year, 1.009; 95% CI, 1.002-1.016). Furthermore, the genotype distribution of IL-10 -819 T/C was completely consistent with that of -592 A/C. These data suggest that IL-10 -819 T/C and -592 A/C may be a promising candidate for an aging-related gene in a Japanese population.     

Association between the IL-4 promoter polymorphisms and asthma or severity of hyperresponsiveness in Taiwanese

BACKGROUND AND OBJECTIVES: Recent family-based studies have revealed a linkage between human chromosome 5q31 and asthma, elevated serum IgE levels and airway hyperresponsiveness (AHR). Among the candidate genes in this region is the gene encoding IL-4. This gene could be a candidate gene for asthma. The aim of this prospective case-control study was to assess the frequency of polymorphisms in the IL-4 gene promoter among asthmatic patients from Taiwan. METHODS: The study consisted of 167 patients with asthma and 111 healthy subjects. PCR amplification followed by Bsm F1 restriction digestion were used to assign genotypes at the IL-4 promoter C-589T locus. Pulmonary function tests, methacholine challenge tests, total IgE, specific IgE antibodies against common inhalant allergens and total eosinophil counts were assessed in asthmatic patients. RESULTS: The T allele frequency for the C-589T IL-4 gene promoter in asthma patients was higher than for normal subjects (P < 0.0001). The frequency discrepancy was found to be even higher for asthmatic patients with severe AHR (P < 0.05). There were no significant differences for the T allele frequency among asthmatic patients with the various other phenotypes such as high versus normal total eosinophil, high versus normal total IgE and high versus normal levels of specific IgE against mite, cockroach or cat dander, or dog dander. CONCLUSIONS: Polymorphism in the promoter of the IL-4 gene is associated with asthma and is a disease modifier in terms of the severity of AHR.     

急性脑梗死患者IL-18基因启动子607C／A、137G／C位点多态性观察

目的观察急性脑梗死患者白细胞介素18（IL-18）基因启动子607C／A和137G／C位点单核苷酸多态性（SNP）。方法采用型特异性引物聚合酶链反应（PCR-SSP）技术检测98例脑梗死患者（观察组）和100例健康对照者（对照组）血清IL-18基因启动子607C／A和137G／C位点多态性。结果两组607C／A位点基因型CC、CA和AA的频率及等位基因频率相比P均〉0．05。观察组组137G／C位点GG型频率显著高于对照组,GC型的频率显著低于对照组（P〈0．05）,两组等位基因频率的分布也有显著性差异（P〈0．05）。结论急性脑梗死患者IL-18基因启动子607C／A位点SNP与脑梗死无关,137G／C位点携带等位基因C可能有预防急性脑梗死的作用。     

Association of G-308A TNF-alpha polymorphism with bronchial asthma in a North Indian population.

Bronchial asthma is an inflammatory disorder in which genetic and environmental factors play an important role. Several susceptible genes have been identified using whole genome scan and candidate gene approaches. Tumor necrosis factor alpha, a pro-inflammatory cytokine, is one such gene that figures prominently in such investigations. The secreted levels of this cytokine are under genetic control and attributed to the presence of single nucleotide polymorphism G-308 A in the promoter region of its gene. However, the association of this polymorphism varies from population to population. As there are no data available on North Indians, the present study aims to fill this void. For this, 366 subjects (155 asthmatic and 211 normal control subject) were genotyped using Amplification Refractory Mutation System Analysis (ARMS-PCR) and agarose gel electrophoresis. The distribution of G/A alleles between the two groups revealed statistically significant differences (p = 0.016). Furthermore, the asthma patients categorized on the basis of pattern (Seasonal versus Perennial) and age of onset of disease (Childhood versus Late Onset) revealed significant association with only seasonal (p = 0.021) and late onset asthmatic groups (p = 0.039). The data from the present study strongly suggest an association between TNF-alpha and asthma in the North Indian population.     

Association of IL-10 -819C/T, -592A/C polymorphisms with the risk of preeclampsia: An updated meta-analysis

Objective:The purpose of our study was to investigate whether IL-10 -819C/T, -592A/C polymorphisms were associated with preeclampsia (PE) susceptibility.Methods:A comprehensive and systematic literature search was performed through online databases, including Web of Science, PubMed, EMBASE, and Chinese databases. Then eligible literatures were included according to inclusion criteria and exclusion criteria. Statistical data analysis was performed using Stata 10.0 software. Odds ratios (OR) and 95% confidence interval were applied to evaluated the association between IL-10 -819C/T, -592A/C polymorphisms and PE susceptibility.Results:According to inclusion and exclusion criteria, 9 case-control studies, including 1423 cases and 2031 controls, were included in this meta-analysis. Our meta-analysis revealed that no association was found between IL-10 -819C/T, -592A/C polymorphisms and the risk of PE in our study.Conclusion:Our meta-analysis suggested that IL-10 -819C/T and -592A/C polymorphisms had no association with PE susceptibility, but had a significant association with PE susceptibility in Asian and Caucasian.     

IL-18启动子区-137G/C和-607C/A位点多态性与结核病易感性关系——Meta分析

目的 应用Meta分析探讨IL-18基因启动子区单核苷酸多态性（single nucleotide polymorphism,SNP）等位基因位点-137和 -607与结核病易感性的关系。方法 收集采用序列特异性引物聚合酶链反应（PCR-SSP）及测序技术检测SNP位点-137和 -607的研究,在严格的质量评价基础上,通过统计学方法应用Review Manager 5.0软件进行了Meta分析。入选文献标准：(1)关于IL-18启动子区SNP -137 G/C和(或) -607 C/A与结核易感性关联的病例-对照研究;（2）对照组基因分布符合Hardy-Weinberg（H-W）遗传平衡定律;（3）原始资料完整;（4）文献中提供基因型频率或等位基因频率;（5）纳入文献语言为中文或英文;（6）多态性检测方法通过PCR-SSP及测序技术或SNaPshot SNP分型方法。文献排除标准：（1）重复报告的研究;（2）数据不清或等位基因不清的文献;（3）基于家系的研究;（4）对照组基因分布没有进行H-W遗传平衡检验的研究。结果 IL-18启动子区SNP -607 C/A位点研究6项,患者695例,正常对照879例;SNP -137 G/C位点研究5项,患者594例,正常对照781例。结核病组IL-18启动子区等位基因-137 G和 -607 C与对照组相比,等位基因-137 C和 -607 A的合并OR值分别为1.41（95% CI为1.15～1.74,P=0.001）和0.93（95% CI为0.81～1.08,P=0.36）。结论 IL-18启动子区SNP位点-137 G/C与结核病易感性相关联,提示IL-18启动子SNP（-137）是结核病的易感位点之一; SNP位点-607 C/A与结核病易感性之间关联无统计学意义。     

Tumor necrosis factor-alpha promoter -308 A/G polymorphism and rheumatoid arthritis susceptibility: a metaanalysis

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) promoter -308 A/G polymorphism has been reported to be associated with rheumatoid arthritis (RA) with inconsistent results. We investigated whether TNF-alpha -308 A/G polymorphism confers susceptibility to RA. METHODS: We conducted a random effect metaanalysis on the association of genotypes A/A (recessive effect), A/A + A/G (dominant effect), A allele, and A/A vs G/G genotypes of the TNF-alpha -308 polymorphisms with RA overall and within different ethnic populations. RESULTS: Fourteen studies, 10 of Europeans, 3 of Latin Americans, and one Asian, were included in this metaanalysis. An association between RA and the TNF-alpha -308 A allele was not found in the overall population (OR 1.005, 95% CI 0.715-1.412, p = 0.976). However, stratification by ethnicity indicated that the TNF-alpha A allele was significantly associated with RA in Latin Americans (OR 2.004, 95% CI 1.158-3.467, p = 0.013). Conversely, there was no association detected for the TNF-alpha A allele with RA patients from the European samples (OR 0.911, 95% CI 0.684-1.212, p = 0.520). The OR for the A/A + A/G genotype, the A/A genotypes, and the A/A vs G/G genotypes in samples overall and in each ethnic group showed a similar trend to those for the TNF-alpha A allele. CONCLUSION: This metaanalysis demonstrates that the TNF-alpha -308 A/G polymorphism may represent a significant risk factor for RA in Latin Americans, but not in Europeans.     

女性护骨素基因启动子区G209A与T245G多态性和骨密度及骨转换的关系

研究护骨素基因启动子区G209A与T245G多态性和女性骨密度及骨转换生化指标的关系，结果显示G209A与T245G多态性和骨密度及骨转换生化指标无关。     

IL-6基因启动子区-634C/G多态性与糖尿病肾病的相关性

目的 探讨白细胞介素6（IL-6）基因启动子区-634C／G多态性与糖尿病肾病（DN）的关系。方法 在昆明地区汉族人中，应用PCR—RFLP方法和等位特异PCR（ASPCR）方法，对246例2型糖尿病（T2DM）患者（正常白蛋白尿组88例，微量白蛋白尿组93例，大量白蛋白尿组65例）和101例健康对照者（NC组）的IL-6基因启动子区-634C／G多态性进行检测。结果 （1）微量白蛋白尿组、大量白蛋白尿组、微量、大量白蛋白尿组的G／G基因型频率均高于正常白蛋白尿组（P=0．001），大量白蛋白尿组亦高于微量白蛋白尿组（P=0．045）。（2）大量白蛋白尿组和大量、微量白蛋白尿组的G等位基因频率均高于正常白蛋白尿组（P=0．031），大量白蛋白尿组亦高于微量白蛋白尿组（P=0．005）。（3）T2DM组中，GG基因型组UAER明显高于CG、CC基因型组（P〈0．01）。（4）Logistic回归分析表明：IL-6基因启动子区-634G／G基因型、病程是DN发生的危险因素。结论在昆明地区汉族人中，IL-6基因启动子区-634G／G基因型可能是DN发生的危险因素，此基因型携带者UAER明显增高；G等位基因可能是DN发展的危险因素之-。     

CTLA-4 gene polymorphisms (-318C/T, +49A/G, +6230A/G) in Iranian patients with multiple sclerosis

Multiple sclerosis (MS) is a disease of the central nervous system (CNS) characterized by multiple regions of demyelination and inflammation along axons with a T cell-mediated autoimmune etiology. While the cytotoxic T lymphocyte antigen 4 (CTLA-4) gene seems to be a strong candidate gene in autoimmune diseases, we investigated its association with a group of patients with MS. One hundred and thirty five patients with relapsing-remitting form of MS and 135 healthy subjects were enrolled in this study. Three single nucleotide polymorphisms (SNPs) (-318C/T, +49A/G, +6230A/G) of the CTLA-4 gene were assessed using PCR-RFLP method. The genotypes -318 CC (82.9% in patients vs. 76.2% in controls) and +49 AA (31.1% in patients vs. 28.1% in controls) were overrepresented in the patient group; however, these differences were not statistically significant. In spite of some previous reports, this study did not confirm any significant association with alleles and genotypes of SNPs of the CTLA4 in Iranian MS patients. Such disparity could be due to genetic background, ethnicity and different forms of the disease.     

Association of interleukin-8 (IL-8 or CXCL8) -251T/A and CXCR2 +1208C/T gene polymorphisms with breast cancer

A case-control study involving 257 breast cancer patients with invasive ductal carcinoma and 233 healthy women was carried out to explore if the IL-8 -251T/A polymorphism and the CXCR2 +1208 C/T polymorphism have a role in breast cancer susceptibility. Genotypic analysis showed an increased frequency of high producer IL-8 -251AA genotype (p=0.016) in the patient group as compared to controls while CXCR2 +1208 C/T polymorphism did not show any differences between studied groups. However, in contrast to IL-8 -251 polymorphism, the percentage of CXCR2 +1208 TT genotype was significantly lower in patients with NPI3.4 (2% and 12%, respectively; p=0.03). Also, ER- tumors showed an approximately significant higher CXCR2 +1208 TT genotype compared to ER+ tumors (18.6% and 7.1%, respectively; p=0.07). In conclusion, IL-8 -251T/A polymorphism is associated with development of invasive ductal carcinoma type of breast cancer while CXCR2 +1208C/T polymorphism may affect the disease progression.     

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

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

High beryllium-stimulated TNF-alpha is associated with the -308 TNF-alpha promoter polymorphism and with clinical severity in chronic beryllium disease.

Beryllium (Be)-antigen stimulates tumor necrosis factor-alpha (TNF-alpha) from bronchoalveolar lavage (BAL) cells in chronic beryllium disease (CBD). This study tested the hypothesis that high concentrations of Be-stimulated TNF-alpha are related to polymorphisms in the TNF-alpha promoter and clinical markers of disease severity in CBD. Demographic and clinical information was obtained from patients with CBD (n = 20). TNF-alpha concentrations were measured in BAL cell culture supernatant by ELISA. A priori, we categorized CBD subjects as either high or low TNF-alpha producers using a cutoff of 1,500 pg/ml. The TNF-alpha promoter sequence, +64 to -1045, was determined by direct sequencing. Human leukocyte-associated antigen (HLA)-DPB1 and -DRB1 genotyping was determined by polymerase chain reaction (PCR). High Be-stimulated TNF-alpha was associated with TNF2 alleles, Hispanic ethnicity, presence of HLA-DPB1 Glu69, and absence of HLA-DR4. Be-stimulated TNF-alpha concentrations correlated with markers of disease severity, including chest radiograph, beryllium lymphocyte proliferation, and spirometry. We found no novel TNF-alpha promoter polymorphisms. These data suggest that the TNF2 A allele at -308 in the TNF-alpha promoter region is a functional polymorphism, associated with a high level of Be-antigen-stimulated TNF-alpha and that these high TNF-alpha levels indicate disease severity in CBD.     

肿瘤坏死因子-α基因多态性与支气管哮喘相关性研究

目的探讨肿瘤坏死因子-α(TNF-α)-308基因多态性与中国汉族支气管哮喘(BA)易感性的关系.方法采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,检测64例BA患者及80例健康对照者的TNF-α-308基因多态性,用Logistic回归计算其比值比(OR)及95%可信区间(95%CI).结果 TNF-α-308A等位基因在BA组及对照组的频率分别为20.31%、8.75%,两组比较有显著性差异;OR值为2.389,95%CI为1.148～5.638.结论 TNF-α-308基因多态性与中国汉族BA易感性有关.     

The SNPs (-1654C/T, -1641A/G and -1476A/T) of protein C promoter are associated with susceptibility to pulmonary thromboembolism in a Chinese population

Background

Pulmonary thromboembolism (PTE) is a common and potentially lethal disease. It is significant to investigate the gene mutations of protein C for clarifying the etiology of PTE. In this present study, we investigated the promoter region polymorphism sites including -1654C/T, -1641A/G and -1476A/T of the protein C gene in a Chinese population.

Methods

A total of 110 cases of PTE and one hundred and ninety healthy controls in a Chinese population were genotyped for three polymorphisms (-1654C/T, -1641A/G and -1476A/T) of the protein C promoter. The statistical analysis was performed by Stata 11.0.

Results

The single nucleotide polymorphisms (SNPs) (-1654C/T, -1641A/G and -1476A/T) in protein C gene were associated with the susceptibility to PTE in Chinese population. According to the binary logistic regression analysis, the independently significant risk factors for PTE were the complications of deep vein thrombosis (DVT) or cancer, history of operation or injury, and the homozygous carriers of the TT genotype (protein C -1654C/T).

Conclusions

The SNPs (-1654C/T, -1641A/G and -1476A/T) of protein C promoter gene are associated with the susceptibility to PTE in a Chinese population. Especially, the homozygous carriers of genotype TT (-1654C/T) increase the risk of PTE in a Chinese population. Confirmation of our preliminary observations in a larger scale study is needed.