Association between promoter variants of interleukin-18 and schizophrenia in a Han Chinese population

An increasing amount of evidence suggests that interleukin-18 (IL-18) plays a pivotal role in the pathophysiology of schizophrenia. However, association between single nucleotide polymorphism of IL-18 and the risk of schizophrenia has not been clarified. This study examined whether two promoter polymorphisms -137 G/C (rs187238) and -607 C/A (rs1946518) of IL-18 were associated with schizophrenia and six clinical symptoms (disorder of perception, thought disorder, disturbance of emotion, disorder of behavior and volition, suicide action, and aggressive action) to provide data for screening high-risk Han Chinese individuals. Three hundred seventy-two schizophrenic patients and 353 healthy controls from a Han Chinese population were examined to assess their genotype and allele frequencies of the two promoter polymorphisms of IL-18. The genotype distributions in both patients and controls were within Hardy-Weinberg equilibrium. No significant differences were observed in the genotype or the allele frequencies of the two single-nucleotide polymorphisms between patients and controls. However, genotype frequencies of -607 C/A showed significant differences between patients and controls in the appearance of perception disorder (χ2 = 6.153, p = 0.046). A significant difference was detected in -137 G/C between patients and controls in the appearance of aggressive action (χ2 = 3.909, p = 0.048). In conclusion, IL-18 gene promoter polymorphisms may not contribute to the susceptibility of schizophrenia in a Han Chinese population, but two single-nucleotide polymorphisms, -137 G/C and -607 C/A, may play a role in the development of perception disorder and aggressive action, respectively.     

IL-6 -174G/C polymorphism and IL-6 serum levels in patients with liver cirrhosis and hepatocellular carcinoma

Recently, a link between high levels of circulating IL-6 and hepatocellular carcinoma (HCC) has been proposed. In addition, single nucleotide polymorphisms (SNPs) in the promoter region of the IL-6 gene have been reported to be related to several inflammatory-related conditions, including cancer. The purpose of this article is: (1) to evaluate the frequencies of SNPs in the IL-6 promoter region at position -174 and IL-6 serum levels in a group of patients with HCC and underlying liver cirrhosis (LC), and compare them with a group of LC patients without HCC; (2) to determine whether a possible correlation exists between the allelic variations, IL-6 serum levels, and the risk of developing HCC. The study included 105 HCC and 95 LC patients. Genomic DNA was isolated using commercially available kits. DNA samples were typed for relevant SNPs of the IL-6 promoter region (-174?G>C, G allele being associated with higher levels of the cytokine). The Restriction Fragment Length Polymorphism (RFLP-PCR) method was used to type the SNPs. IL-6 serum levels were determined using an ultrasensitive commercially available ELISA kit. IL-6 serum levels were higher in G/G compared to C/C genotypes only in HCC (z=2; p=0.04) and G/G versus G/C (z=1.8; p<0.03). IL-6 serum levels in G carriers (G/G+G/C) were higher in HCC 4.8 (0.2-17.5) versus LC patients 2.2 (0.07-11.5) (z=2.8; p=0.004). There was no difference for genotype C/C. IL-6 serum levels in HCC correlated with G carriers (G/G+G/C) (ρ=0.25, p=0.05). A positive correlation was also found between sIL-6 levels and some parameters of liver function both in LC and in HCC patients.     

Genetic variants of IL6 gene promoter influence on C-reactive protein levels but are not associated with susceptibility to invasive pulmonary aspergillosis in haematological patients

Several lines of evidence indicate that IL6 plays a major role in the pathogenesis of a number of infectious diseases. The purpose of this study was to determine whether IL6 promoter polymorphisms were genetic markers of susceptibility to invasive pulmonary aspergillosis (IPA). To clarify the relationship between IL6 variants and IPA susceptibility, the IL6−174(G/C) and IL6−634(G/C) promoter single nucleotide polymorphisms (SNPs) were defined and plasma concentrations of IL6 and C-reactive protein (CRP) were measured. The study included 130 patients with haematological malignancies and 145 unrelated healthy individuals. No significant genotypic and allelic differences were found between patients and healthy controls. IPA was diagnosed in 71 of 130 patients according to the consensus criteria. CRP values were significantly associated with both IL6−174(G/C) and IL6−634(G/C) polymorphisms. However, IL6 and CRP values were similar between IPA and non-IPA groups. Neither IL6−174(G/C) nor IL6−634(G/C) polymorphisms were associated with IPA infection (p = 0.414 and p = 0.184, respectively). No evidence of association was found between allelic frequencies of IL6 promoter polymorphisms and IPA infection (p = 0.864 and p = 0.104, respectively). Further, no association was detected between IL6 genotypes and clinical profiles in IPA patients. Haplotype analysis also revealed that IL6 gene was not associated with IPA susceptibility in a Spanish population (Global haplotype association p value: 0.31). These findings suggest that IL6 polymorphisms influence on CRP circulating levels but are not associated with IPA susceptibility. Because the sample size is relatively small in our series, larger investigations of IL6−174(G/C)/IL6−634(G/C) genotypes and haplotypes are needed to clarify the potential role of this gene in the pathophysiology of IPA infection.     

Influence of the -308 TNF-alpha and -174 IL-6 polymorphisms on lipid profile in Mexican subjects

Polymorphisms in the promoter region of several cytokine genes have been associated with differential cytokine production. Several reports indicate that polymorphisms in the tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) genes are associated with lipid abnormalities. The aim of this study was to identify the genotype frequencies for -308G/ATNF-alpha and -174G/CIL-6 polymorphisms in Mexican subjects and to determine the influence of both polymorphisms on serum lipid levels. Serum lipid concentrations were measured in 100 healthy Mexican subjects. Screening of the -308G/ATNF-alpha and -174G/CIL-6 polymorphisms was performed in all participants using PCR-RFLPs. Genotype frequency for TNF-alpha polymorphism was: 87% GG and 13% GA, whereas IL-6 polymorphism was: 77% GG and 23% GC. The polymorphism frequencies obtained in this study were significantly different to Caucasian populations. High serum levels of triglycerides and total cholesterol were associated with GG genotype of the -308 TNF-alpha polymorphism, as well as low HDL-c levels, but no association was found between the -174 IL-6 polymorphism and serum lipid concentrations. We observed a significant association of the -308 TNF-alpha polymorphism with lipid profile in Mexican subjects. Furthermore, the genotype distribution of -308 TNF-alpha and -174 IL-6 polymorphisms in Mexican Mestizo population similar to populations in different continents may be due to our genetic background influenced by the mixture of Spaniards, Indian and black genes.     

Four novel single nucleotide polymorphisms within the promoter region of p53 gene and their associations with uterine leiomyoma

Dysregulated p53 expression has been implicated as a major contributor to numerous tumorigenesis. Single nucleotide polymorphisms (SNPs) within the functional consequence of the novel p53 promoter region remains obscure. Herein, we aimed to establish the extent of genetic variability within the promoter region of p53 gene as well as their association with leiomyoma susceptibility. Women were divided into two groups, leiomyoma (n = 160) and nonleiomyoma controls (n = 200). Total DNA was isolated from the peripheral blood of subjects. The DNA fragment containing p53 promoter regions (+64 approximately -404 bp) were obtained by amplification of polymerase chain reaction. The variations of DNA fragments were detected by DNA sequencing or restriction fragment length polymorphism (RFLP). Sequence alignment was used to identify sequence variations in p53 promoter regions. Genotypes were analyzed by method of RFLP. Genotypes/allelic frequencies in the leiomyoma and control groups were compared. A total of 15 sequence variations within p53 promoter region were identified, including -408 T/C, -382 A/G, -359 A/G, -325 T/C, -250 A/G, -216 T/C, -205 G/A, -198 G/A, -177 T/C, -103 A/G, -81 G/A, -71 G/A, -51 T/A, -33 A/G, and -17 T/C. Among these variations, four SNPs (-250 A/G, -216 T/C, -103 A/G, and -33 A/G) were established. Allele frequencies of -250*G/-216*C/-103*G/-33*G in the leiomyoma group and control group 6.9/5.0/5.9/3.8% and 3.8/1.8/2.3/4.0%, respectively. Two of them (-216*C and -103*G) are associated with higher leiomyoma susceptibility. We concluded that some sequence variations were observed within the promoter region of p53 gene. The SNPs of -216*C and -103*G among the identical sequence variations are associated with leiomyoma development.     

葡萄糖转运体9（GLUT9）基因启动子区的rs13124007（G/C）及rs6850166（G/A）位点的单核苷酸多态性（SNP）与汉族女性痛风相关性研究（英文）

目的：探讨葡萄糖转运体9（GLUT9）基因启动子区的rs13124007（C/G）及rs6850166（A/G）位点的单核苷酸多态性（SNP）与中国汉族女性人群痛风易感性之间的相关性。方法：选取185例痛风患者和300例正常对照者,提取基因组DNA,采用聚合酶链式反应（PCR技术）,特异性扩增GLUT9基因所需要的目的片段,对扩增的目的片段进行测序后,比较痛风组和正常对照组的基因型频率及等位基因频率分布情况。结果：女性痛风组中GLUT9基因的启动子区rs13124007和rs6805116两个位点的基因型频率分布与正常对照组相比,统计学上无明显的差异（X2=0.906,P=0.636;X2=3.335,P=0.189）,rs13124007 SNP位点的C等位基因频率和rs6850166SNP位点的A的等位基因频率与正常对照组相比也无明显的统计学差异（X2=0.506,P=0.477;X2=3.268,P=0.071）。结论：葡萄糖转运体9（GLUT9）基因启动子区的rs13124007（C/G）及rs6850166（A/G）位点的单核苷酸多态性（SNP）与中国汉族女性人群痛风易感性无明显的相关性。     

Investigation of relationship between IL-6 gene variants and hypertension in Turkish population

Hypertension (HT) is a common and life threating health problem worldwide leading to stroke, heart attack and renal failure. It is characterized by elevated blood pressure forced heart load. Human interleukin-6 (IL-6) and C- reactive protein (CRP) are known to be involved in inflammatory processes. IL-6 gene is a polymorphic gene which −174 G/C is a common and −572 G/C is a rare polymorphisms identified in promoter region. Publications on IL-6 gene polymorphisms raised the question whether this gene polymorphisms lead to susceptibility to HT or not. To investigate the effects of IL-6 gene −174 G/C (rs 1800795) and −572 G/C (rs1800796) polymorphisms on plasma IL-6 and CRP levels and their associations with hypertension disease in Turkish population we analyzed −174 G/C and −572 G/C polymorphisms and plasma IL-6 and CRP levels in 111 healthy controls and 108 hypertension patients from Adıyaman, Turkey. We determined the genotypes using polymerase chain reaction-restriction fragment length polymorphism and analyzed plasma levels of IL-6 by ELISA and CRP by automated standard biochemical methods. We have found no statistically significant differences between IL-6 gene −174 G/C and −572 G/C genotypes and allelic frequencies and IL-6 and CRP plasma levels and HT (p > 0.05). No CC genotype was found in control subjects for −572 G/C polymorphism. In conclusion, we found relation to −174 G/C and −572 G/C gene variants between neither IL-6 and CRP levels nor hypertension. The −572 G allele and GG genotype are predominant in Turkish population in Adıyaman, Turkey whereas the CC genotype is very rare.     

Inhibitor IκBα promoter functional polymorphisms in patients with multiple sclerosis

The aim of this study is to investigate the association of IκBα promoter polymorphisms with the development of Multiple Sclerosis (MS) disease in Iranian population. One hundred and fifty patients with MS along with 150 unrelated healthy controls were enrolled in this study. The IκBα ?881A/G (rs3138053), ?826C/T (rs2233406) and ?519C/T (rs2233408) polymorphisms were determined by the polymerase chain reaction/restriction fragment length polymorphism method. This study demonstrated that the genotype frequencies of IκBα ?881A/G and ?826T/T, and allele frequencies of IκBα?881G were significantly higher in patients with MS with respect to as compared to the controls. We also found that the estimated haplotype frequency of IκBα promoter ?881G–826T–519C was significantly increased in the patient with MS in comparison with that of the healthy individuals. This study reveals that polymorphisms in the IκBα promoter (?881 A/G, ?826 C/T) are strongly associated with the susceptibility of Iranian MS patients.     

A polymorphism in the cyclooxygenase 2 gene in type 1 diabetic patients with nephropathy

Diabetic nephropathy (DN), the most serious complication of Type 1 diabetes (DM1), has a strong genetic component. Cyclooxygenase-2 (COX-2), an inducible enzyme by a number of stimuli, has been implicated in pathophysiology of cardiovascular and renal disease, including DN. The allele -765C, of the -765G > C polymorphism (rs20417) in the COX-2 promoter has lower promoter activity compared with the -765G allele and protective effects in cardiovascular disease. This polymorphism was not investigated in patients with DM1 and nephropathy. The study was conducted in 779 Caucasian patients with DM1 and compared to a representative sample of healthy Czech population. The patients demonstrated lower frequencies of the CC genotype (P = 0.005). From the DM1 cohort, 153 patients met the criteria for low risk of the development of DN (LRDN, duration of DM1 > 10 years, normoalbuminuria, normotension) and 139 patients had manifest DN. There were no differences in -765G > C polymorphisms between LRDN and DN patients. Moreover, the C/G allele frequencies did not also differ between the groups. In conclusion, patients with DM1 display lower freqencies of the protective CC genotype as compared to healthy subjects. However, the study did not reveal associations of -765G > C polymorphism with the risk of DN.     

Racial differences in selected cytokine allelic and genotypic frequencies among healthy,pregnant women in North Carolina

BACKGROUND: Genetic susceptibility to diseases is likely influenced by common DNA variants in the form of single nucleotide polymorphisms (SNPs). The value of SNPs for linkage and association mapping studies may depend on the distribution of SNP allele frequencies across populations. OBJECTIVES: To establish the SNP allelic frequencies among Caucasian and African American women for tumor necrosis factor (TNF)alpha, transforming growth factor (TGF)beta1, interleukin-10 (IL10), interleukin-6 (IL6), and interferon (IFN)gamma. MATERIALS AND METHODS: DNA was extracted from whole blood from 123 healthy, pregnant women. PCR-based genotyping was performed for the genes encoding TNFalpha (-308G/A), TGFbeta1 (codon 10C/T, codon 25C/G), IL10 (-1082A/G, -819T/C, -592A/C), IL6 (-174C/G) and IFNgamma (874T/A). Allele frequencies were determined by Hardy-Weinberg Equilibrium and Linkage Disequilibrium tests. Differences in the SNP allelic frequencies between Caucasians and African Americans were assessed by the chi(2) of Amitage trend test. RESULTS: SNP allelic and genotypic frequencies for IL6 and IFNgamma, but not for TNFalpha, TGFbeta1, and IL10, differed significantly between the Caucasian and African American women. CONCLUSIONS: Recognition of racial differences in SNP allelic and genotypic frequencies for selected cytokines is important for designing and powering future linkage and association mapping studies investigating the role of cytokines in human disease.     

2型糖尿病患者醛糖还原酶基因5′调控区的多态性与功能

 为了探讨醛糖还原酶基因 5′调控区存在的可引起蛋白质表达发生改变的遗传变异及这些变异与糖尿病视网膜病变的相关性 ,应用PCR SSCP分析对醛糖还原酶基因 5′调控区 - 60 9～ + 4 0的DNA片段进行了筛选 .所有变异体均进行DNA序列分析并克隆至氯霉素乙酰转移酶报告基因载体(pCATreportervector) ,然后将重组质粒转染HeLa细胞 ,通过检测氯霉素乙酰转移酶的活性求出启动子的相对活性 .同时进行凝胶滞留试验与足纹分析以确定DNA与核蛋白的相互作用 .结果显示 ,在 1 45名 2型糖尿病患者及 1 2 3名正常对照的醛糖还原酶基因 5′调控区除野生型外 ,共发现 2种多态性 [C( - 1 0 6)T、C( - 1 2 )G].在正常对照与患者中 ,基因型WT WT ,WT C( - 1 2 )G和WT C( - 1 0 6)T的发生率无显著性差异 .在有视网膜并发症与无视网膜并发症的 2型糖尿病患者中 ,WT C( -1 0 6)T的发生率分别为 35 5%和 1 7 9% ( χ2 =4 0 0 ,P <0 0 5) ,WT C( - 1 2 )G的发生率分别为1 5 5%和 3 3% ( χ2 =3 43,P >0 0 5) .在有并发症的患者中 ,WT C( - 1 2 )G和WT C( - 1 0 6)T两者的总发生率为 42 3% ,显著高于无并发症的患者 ( 2 0 0 % ) ( χ2 =6 2 3,P <0 0 2 5) .野生型 ,C( - 1 2 )G和C( - 1 0 6)T等 3种调控序列的相对活性分别为     

肿瘤坏死因子α基因启动子区多态性与皖南地区Graves病发生的关系

目的 探讨肿瘤坏死因子α（TNF-α）基因启动子区-238G/A和-308G/A多态与皖南地区汉族人Graves病（GD）发生的关系.方法 采用Taqman探针等位基因鉴别技术,检测和分析432例Graves病患者和629例正常对照者的TNF-α基因-238G/A和-308G/A多态位点的基因型和等位基因的频率.结果 TNF-α-238G/A和-308G/A多态基因型和等位基因频率在病例组和对照组的分布均无统计学差异（P＞0.05）,根据基因型分组进行临床病理特征比较亦未发现相关性.结论 TNF-α-238G/A和-308G/A多态与皖南地区汉族人GD发病无相关性.     

Transgenic mice with -6A haplotype of the human angiotensinogen gene have increased blood pressure compared with -6G haplotype

Hypertension is a serious risk factor for cardiovascular disease, and the angiotensinogen (AGT) gene locus is associated with human essential hypertension. The human AGT (hAGT) gene has an A/G polymorphism at -6, and the -6A allele is associated with increased blood pressure. However, transgenic mice containing 1.2 kb of the promoter with -6A of the hAGT gene show neither increased plasma AGT level nor increased blood pressure compared with -6G. We have found that the hAGT gene has three additional SNPs (A/G at -1670, C/G at -1562, and T/G at -1561). Variants -1670A, -1562C, and -1561T almost always occur with -6A, and variants -1670G, -1562G, and -1561G almost always occur with -6G. Therefore, the hAGT gene may be subdivided into either -6A or -6G haplotypes. We show that these polymorphisms affect the binding of HNF-1α and glucocorticoid receptor to the promoter, and a reporter construct containing a 1.8-kb hAGT gene promoter with -6A haplotype has 4-fold increased glucocorticoid-induced promoter activity as compared with -6G haplotype. In order to understand the physiological significance of these haplotypes in an in vivo situation, we have generated double transgenic mice containing either the -6A or -6G haplotype of the hAGT gene and the human renin gene. Our ChIP assay shows that HNF-1α and glucocorticoid receptor have stronger affinity for the chromatin obtained from the liver of transgenic mice containing -6A haplotype. Our studies also show that transgenic mice containing -6A haplotype have increased plasma AGT level and increased blood pressure as compared with -6G haplotype. Our studies explain the molecular mechanism involved in association of the -6A allele of the hAGT gene with hypertension.     

Polymorphisms of IL-10 gene in patients infected with HCV under antiviral treatment in southern Brazil

Interleukin-10 (IL-10) is a cytokine that plays an important role in the regulation of the immune system. Gene polymorphisms of IL-10 have been associated with the different expression levels of this cytokine. In hepatitis C virus infection, IL-10 appears to interfere with the progression of disease, viral persistence and the response to therapy. This study investigated genetic variability in the IL-10 gene promoter between patients infected with hepatitis C virus (HCV) and healthy individuals, associating the frequency of polymorphisms with different aspects of viral infection. This is a case-control study with 260 patients who were infected with HCV and 260 healthy individuals. Genotyping of the polymorphisms was performed using the technique of amplification refractory mutation system PCR (ARMS-PCR) for regions of the IL-10 gene promoter (-1082 G/A, -819 C/T, -592 C/A). The frequencies of alleles and genotypes related to polymorphisms in the IL-10 gene promoter showed a higher frequency of the G allele and genotype GG in the -1082 region between the infected group and the control group (p = 0.005 and p = 0.001, respectively), whereas the AA genotype was significantly more frequent in the control group. The frequencies of the haplotypes GTA and GCC were higher in the group of infected individuals, whereas the haplotype ATA was more frequent in the healthy group (p < 0.006). It was also observed that the genotypes GG and AG in the region -1082 were significantly more frequent among patients infected with HCV who were in advanced stages of fibrosis and cirrhosis (p = 0.042). No association was observed between polymorphisms of IL-10 and sustained virologic response (SVR).     

Relations of APOE promoter polymorphisms to LDL cholesterol and markers of subclinical atherosclerosis in young adults

The common apolipoprotein E (apoE) gene (APOE) epsilon2/epsilon3/epsilon4 polymorphism explains part of serum lipid variation, and polymorphisms in the APOE promoter region have been proposed to participate in the regulation of serum lipid levels within the most common APOE epsilon3/epsilon3 genotype group. We determined APOE -219G/T and +113G/C promoter genotypes and estimated APOE haplotypes in 525 participants of the Cardiovascular Risk in Young Finns Study. We studied the associations of the APOE promoter polymorphisms and their haplotypes with cross-sectional and longitudinal serum lipid and apolipoprotein concentrations as well as with flow-mediated dilatation (FMD), carotid artery compliance (CAC), and intima-media thickness (IMT) within the APOE epsilon3/epsilon3 carriers. We found no significant association between the APOE promoter genotypes and serum lipids [low density lipoprotein-cholesterol (LDL-C), HDL-C, and triglycerides], apolipoproteins (apoA-I and apoB), or brachial artery FMD, CAC, or carotid IMT in either men or women. In longitudinal analyses in males, the carriers of heterozygous genotypes (-219G/T or +113G/C) and, furthermore, carriers of the -219T/+113C/epsilon3 haplotype had significantly higher LDL-C and total cholesterol concentrations throughout the 21 year follow-up period compared with homozygous G allele carriers or noncarriers of the -219T/+113C/epsilon3 haplotype. Such associations were not found in females. In summary, the APOE promoter polymorphisms -219G/T and +113G/C as well as their haplotype are associated with longitudinal changes in LDL-C and total cholesterol concentrations in young Finnish males but do not seem to be major determinants for FMD, CAC, or carotid IMT in males or females.     

中国广东汉族人群核苷酸修复基因hMTH1 遗传多态性研究

为研究中国南方汉族人群核苷酸修复基因hMTH1遗传多态性,应用聚合酶链反应-单链构象多态性技术检测172名健康人外周血白细胞hMTH1基因启动子及全部5个外显子多态性,并进行DNA测序。结果发现hMTH1基因启动子及外显子1序列保守,未见突变;外显子2第73位碱基存在T→C杂合型突变,基因型TT和TC频率分别为93.02%、6.98%,等位基因T和C频率分别为96.51%、3.49％;外显子3第45位遗传密码存在T→C杂合型突变,基因型TT和TC频率分别为95.35%、4.65%,等位基因T和C频率分别为97.67%、2.33%,该多态性为首次发现;外显子4第83位遗传密码存在G→A杂合型突变,基因型GG和GA频率分别为89.53%、10.47%,等位基因G和A频率分别为94.77%、5.23％;外显子5第119位氨基酸遗传密码存在C→T杂合型突变,基因型CC和CT频率分别为95.93%、4.07%,等位基因C和T频率分别为97.97%、2.03％。Abstract: In order to study the genetic polymorphisms of nucleotide repair gene hMTH1 in southern Chinese Han population, the polymorphisms of the gene’s promoter and its five exons among peripheral blood lymphocytes of 172 Chinese Han people were analyzed with polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing. The sequences of the promoter and exon 1 of hMTH1 gene were conserved. A T to C polymorphism was detected at the 73th base in exon2. The genotype frequencies of TT and TC were 93.02% and 6.98%, respectively. The allelic frequencies of T and C were 96.51% and 3.49％, respectively. A T to C polymorphism was detected at codon 45 in exon3, which was first reported. The genotype frequencies of TT and TC were 95.35% and 4.65%, respectively. The allelic frequencies of T and C were 97.67% and 2.33%, respectively. A G to A polymorphism was detected at codon 83 in exon4. The genotype frequencies of GG and GA were 89.53% and 10.47%, respectively. The allelic frequencies of G and A were 94.77% and 5.23％, respectively. A C to T polymorphism was detected at codon 119 in exon5. The genotype frequencies of CC and CT were 95.93% and 4.07%, respectively. The allelic frequencies of C and T were 97.97% and 2.03％, respectively.     

Genetic polymorphisms of the interleukin-18 gene and risk of prostate cancer

Genetic factors are known to be important in the development of prostate cancer. Interleukin-18 (IL-18) is a multifunctional cytokine that induces interferon-gamma secretion and plays an important role in antitumor immunity. Variations in the DNA sequence in the IL-18 gene promoter may lead to altered IL-18 production and/or activity, and so this can modulate an individual's susceptibility to prostate cancer. To test this hypothesis, we investigated the relationship of IL-18 gene promoter -137 G/C and -607 C/A polymorphisms and their haplotypes with the risk of prostate cancer. We analyzed two single nucleotide polymorphisms of IL-18 gene promoter -137 G/C and -607 C/A in 265 patients with prostate cancer and 280 age- and sex-matched controls, using sequence-specific primers-polymerase chain reaction strategy. There were significant differences in the genotype and allele distribution of -137 G/C polymorphism of the IL-18 gene among cases and controls. The -137 GC and CC genotypes were associated with a significantly increased risk of prostate cancer as compared with the -137 GG genotypes [odds ratio (OR) = 1.721; 95% confidence interval (CI): 1.187-2.496; p = 0.004, and OR = 2.181; 95% CI: 1.034-4.603; p = 0.037, for GC and CC, respectively]. Consistent with the results of the genotyping analyses, the -137C/-607A haplotype was associated with a significantly increased risk of prostate cancer as compared with the -137G/-607C haplotype (OR = 1.544; 95% CI, 1.137-2.096; p = 0.005). This study shows for the first time an association between IL-18 gene promoter -137 G/C polymorphism and prostate cancer in a Chinese population.