Analysis of vitamin D receptor gene (VDR) polymorphisms in Turner syndrome patients

Individuals with Turner syndrome (TS) have increased risk for autoimmune diseases, especially thyroid abnormalities. The function of the vitamin D receptor (VDR) gene is influenced by several genetic polymorphisms which are associated with a susceptibility to a range of autoimmune diseases. Thus, we have hypothesized a possible relationship between thyroid abnormalities and VDR polymorphisms (ApaI/G1025-49T, TaqI/T1056C, FokI/T2C and BsmI G1024?+?283A) in TS patients. A case-control study was performed comprising 101 Brazilian women with TS and a control group consisting of 133 healthy fertile women without a history of autoimmune diseases. In TS group, 21.8% had Hashimoto’s thyroiditis. Detection of VDR polymorphisms was performed using TaqMan system by real-time PCR. The χ² was used to compare allele and genotype frequencies between groups. Combined genotypes of VDR gene polymorphisms were assessed by the haplotype analysis. A p value <0.05 was considered statistically significant. Relatively similar VDR polymorphisms genotype and allelic frequencies in cases and controls were found, even when only considering the patients with thyroid abnormalities. Haplotype analysis showed that none of the VDR haplotypes were associated to thyroid diseases in TS patients. In conclusion, the results showed no association between VDR gene polymorphisms and thyroid abnormalities in Brazilian TS patients tested.     

Vitamin D receptor gene polymorphisms and risk of polycystic ovary syndrome in South Indian women

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of reproductive age women. Emerging evidence suggests that Vitamin D Receptor (VDR) might be a causal factor for characteristics associated with PCOS such as obesity and type 2 diabetes. Present study investigated association between VDR gene BsmI A/G (rs1544410), ApaI A/C (rs7975232) and TaqI T/C (rs731236) single nucleotide polymorphisms and PCOS risk in South Indian women. Genotyping of VDR gene SNPs was carried out in PCOS patients (n?=?95) and controls (n?=?130) by PCR-RFLP method and confirmed by sequencing analysis. Haplotype frequencies for multiple loci and the standardized disequilibrium coefficient (D′) for pairwise linkage disequilibrium (LD) were assessed by Haploview software. Results showed significantly increased frequencies of BsmI G/G (p?=?.0197), ApaI C/C (p?=?.048), TaqI C/C (p?=?.044) genotypes and BsmI G (p?=?.0181), ApaI C (p?=?.0092), TaqI C (p?=?.0066) alleles in patients compared to controls. In addition, the frequency of the ‘BsmI G, ApaI C, TaqI C’ haplotype was also significantly elevated in patients (p?=?.0087). In conclusion, the VDR gene BsmI A/G ApaI A/C TaqI T/C and haplotype may constitute an inheritable risk factor for PCOS in South Indian women.     

Association study of vascular endothelial growth factor gene polymorphisms in endometrial carcinomas in a Japanese population

OBJECTIVE: Vascular endothelial growth factor (VEGF) is one of the most potent endothelial cell mitogens and plays a critical role in angiogenesis of endometrial carcinomas. Several studies have demonstrated positive associations between VEGF gene polymorphisms and several carcinomas. In this study we investigated whether VEGF gene polymorphisms are associated with endometrial carcinomas in a Japanese population. METHODS: The allele frequencies and genotype distributions of VEGF -460 C/T, +405 G/C, and +936 C/T polymorphisms were examined in 105 endometrial carcinomas and 179 controls using PCR-RFLP analysis. An association of these polymorphisms with three-year disease-free survival was evaluated using the Kaplan-Meier method. RESULTS: No significant differences in the allele frequencies and genotype distributions of VEGF -460 C/T (p = 0.54, 0.90), +405 G/C (p = 0.31, 0.17), and +936 C/T polymorphisms (p = 0.46, 0.24) were observed between endometrial carcinoma patients and controls. There were no significant differences in the frequencies of haplotype -460 T/+405 C between patients and controls. Futhermore, VEGF -460 C/T, +405 G/C, and +936 C/T polymorphisms were not associated with three-year disease-free survival of endometrial carcinoma patients. CONCLUSIONS: Although limited by sample size, our study did not demonstrated any evidence that VEGF -460 C/T, +405 G/C, and +936 C/T polymorphisms are associated with an increased risk of endometrial carcinomas in Japanese women.     

亚甲基四氢叶酸还原酶、凝血因子V和凝血酶原基因多态性与原因不明复发性早期流产的关系

目的探讨亚甲基四氢叶酸还原酶（MTHFR）基因C677T突变、凝血因子V（FV）基因G1691A突变和凝血酶原（PT）基因G20210A突变与原因不明复发性早期流产（URESA）的关系。方法应用聚合酶链反应．限制性片段长度多态性（PCR-RFLP）技术分析112例URESA患者（病例组）和100例健康妇女（对照组）MTHFR、FV和PT3种基因多态性。结果（1）MTHFR基因的T／T基因型和T等位基因频率,病例组[分别为38．4％（43／112）和59．8％（134／224）]高于对照组[分别为18．0％（18／100）和43．0％（86／200）],两组分别比较,差异均有统计学意义（P＜0．01）。病例组与对照组比较,T／T基因型者发生URESA的相对风险增加（OR=2．8390,95％CI为1．5022～5．3661）。（2）病例组和对照组妇女Fv基因和PT基因均为G／G基因型（即正常带型）。结论MTHFR基因C677T位点多态性与URESA发病密切相关,T／T基因型是其发病的危险因素。FV和PT基因的突变率在中国妇女人群中极低。     

骨保护素基因多态性与重度子痫前期发病的关系

目的 探讨骨保护素基因启动子区163A/G和950T/C位点的多态性与重度子痫前期发病的关系.方法 选择2007年7月-2009年3月在四川大学华西第二医院就诊的成都市汉族孕妇共166例.其中重度子痫前期孕妇85例(重度子痫前期组),健康足月孕妇81例(对照组).应用PCR限制性片段长度多态性(RFLP)技术测定两组孕妇骨保护素基因启动子区163A/G和950T/C位点的基因型及等位基因频率,对两组中不同等位基因孕妇的血压、血肌酐、24 h尿蛋白定量、新生儿出生体质量等临床指标进行比较.结果(1)骨保护素基因启动子区163A/G、950T/C位点的基因型及等位基因频率在两组孕妇中的分布均符合Hardy-Weinberg遗传平衡定律.163A/G位点的基因型为AA、AG、GG,等位基因为A、G;950T/C位点的基因型为TT、TC、CC,等位基因为T、C.(2)重度子痫前期组孕妇163A/G、950T/C位点的基因型、等位基因频率与对照组比较,差异均无统计学意义(P＞0.05).(3)重度子痫前期组中163A/G位点AG+ GG基因型孕妇血肌酐水平[(76±24)μmol/L]明显高于AA基因型孕妇[(56±18)μmol/L],而新生儿出生体质量[(2040±721)g]显著低于AA基因型孕妇[(2520±810)g],两者比较,差异均有统计学意义(P＜0.05).对照组中163A/G位点的AG+ GG基因型孕妇血尿素、血肌酐、新生儿出生体质量、新生儿身长等临床指标与AA基因型孕妇比较,差异均无统计学意义(P＞0.05).(4)重度子痫前期组中950T/C位点的TT基因型孕妇收缩压[(153±16)mm Hg(1 mm Hg =0.133 kPa)]、24 h尿蛋白定量[(4.0±2.5)g]均显著高于TC+ CC基因型孕妇[分别为(145±17)mmHg及(2.9±1.8)g],两者比较,差异均有统计学意义(P＜0.05);而对照组中950T/C位点的不同基因型孕妇各临床指标之间比较,差异均无统计学意义(P＞0.05).结论 携带163A/G位点的G等位基因孕妇比携带A等位基因者更具有重度子痫前期遗传易感性;携带950T/C位点的T等位基因孕妇比携带C等位基因者也更具有重度子痫前期遗传易感性.提示骨保护素基因多态性可能与重度子痫前期的发病有关.     

淄博市汉族女性亚甲基四氢叶酸还原酶和甲硫氨酸合成酶还原酶基因多态性分布研究

目的:分析淄博市汉族女性亚甲基四氢叶酸还原酶(MTHFR)C677T、A1298C及甲硫氨酸合成酶还原酶(MTRR)A66G基因多态性的分布特征。方法:采用横断面调查研究方法,以淄博市1041例汉族女性为研究对象,采集口腔黏膜上皮细胞,提取基因组DNA,采用Taqman-MGB技术检测MTHFR和MTRR基因多态性。统计分析基因多态性的分布特征,并与已报道的其他地区数据进行比较。结果:淄博市汉族女性的MTHFR 677TT纯合突变基因型频率为43.6%,显著高于郑州、德阳、海南地区(P<0.01);MTHFR 1298CC纯合突变基因型频率为1.4%,显著低于德阳和海南地区(P<0.01)。MTRR 66GG纯合突变基因型频率为4.8%,显著低于海南地区(P<0.01)。结论:淄博市汉族女性有不同于其他地区的MTHFR和MTRR基因多态性分布特征。     

维生素D受体基因多态性与中国汉族儿童结核病易感性的研究

目的　探讨维生素D受体（VDR）基因多态性与中国汉族儿童结核病易感性的关系。 方法　收集2005年1月至2008年3月北京儿童医院收治的125例汉族儿童 结核病患儿,以同期在北京儿童医院门诊行外科手术（如疝、牙齿矫正、鞘膜积液等）前查体的446例患儿作为对照,对照组无结核病史,X线胸片无异常,PPD皮 试硬结直径小于5 mm,按照年龄、性别以及居住地与病例组进行匹配,采用聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）检测VDR基因上的Fok I和Taq I位点多态性,采用SPSS 12.0软件对病例组和对照组的基因型和等位基因频率进行卡方检验。 结果　结核组和对照组Fok I位点的FF、Ff、ff基因型频率分别为 29.6%、51.2%、19.2%和27.6%、50.9%、21.5%;Taq I位点的TT、Tt、tt基因型频率分别为90.4%、9.6%、0和86.8%、13.0%、0.2%;结核组和对照组在基因型频率 和等位基因频率分布上差异均无统计学意义。将样本按性别进行分组比较后发现,不同性别中病例组和对照组儿童的基因型和等位基因频率之间的差异无统计学 意义。 结论　VDR基因上的Fok I和Taq I位点的多态性与中国汉族儿童结核病的易感性无明显相关性。     

Epidermal growth factor receptor and human epidermal growth factor receptor 2 gene polymorphisms in endometrial cancer in a Japanese population

Endometrial cancer is associated with both EGFR and HER2 receptor activation. The EGFR and HER2 genes could be disease susceptibility candidate genes for this cancer. This study was conducted to investigate a possible association between EGFR and HER2 gene polymorphisms and endometrial cancer and the influence of these polymorphisms on the clinical outcome of endometrial cancer patients in a Japanese population. The authors compare the genotype distributions and allele frequencies of the EGFR +2073 A/T and HER2 +655 A/G polymorphisms in 116 endometrial cancer patients and 213 controls using polymerase chain reaction-restriction fragment length polymorphism (RFLP) analysis. RFLP results were confirmed by direct DNA sequencing. Of the 116 patients, 76 (65.5%) could be followed up. Disease-free survival estimates were computed using the Kaplan-Meier method, and differences between survival periods were assessed using the log-rank test. No significant differences were observed in either genotype distributions or allele frequencies in the EGFR +2073 A/T and HER2 +655 A/G polymorphisms between endometrial cancer patients and controls. The stratification by histological types and staging failed to identify significant differences between endometrial cancer patients and controls. No statistical differences were noted between these polymorphisms and disease-free survival (Kaplan-Meier log-rank test P = .55 and .66, for the EGFR +2073 A/T and HER2 +655 A/G, respectively). These results suggest that the EGFR +2073 A/T and HER2 +655 A/G polymorphisms are not associated with endometrial cancer in a Japanese population. These conclusions are based on relatively small numbers and will require verification from additional independent studies.     

Foxp3基因多态性与原因不明复发性自然流产易感性的关系

目的 探讨转录因子Foxp3基因多态性与原因不明复发性自然流产(URSA)易感性的关系.方法 分别采用PCR-限制性片段长度多态性技术(针对Foxp3基因的rs3761548、rs2294021位点)和PCR-等位基因特异性扩增技术(针对rs2232365、rs5902434位点),检测146例URSA患者(URSA组...     

Fas and FasL genetic polymorphisms in women with recurrent pregnancy loss: a case-control study

Aberrant apoptosis at the trophoblast–maternal interface and abnormal expression of Fas and Fas ligand (FasL) have been reported in complicated pregnancies with recurrent pregnancy losses (RPL) and preeclampsia. We assessed the prevalence of Fas and FasL genetic polymorphisms in Korean women with RPL and in fertile controls. In total, 306 women with RPL and 298 fertile controls were enrolled. Genotype distributions of Fas and FasL in RPL patients versus fertile controls were examined under the Hardy–Weinberg equilibrium. Fas ?670 A/G genotype (AA versus AG versus GG, p?=?0.340) and allele frequencies (A versus G, p?=?0.412) were not different between the RPL and control groups. There was no difference in each Fas ?1377?G/A and FasL ?844 C/T genotype, and their allele frequencies. In addition, the unions of two zygosities of each genotype and their combined genotypes did not differ between two groups. No difference in the prevalence of Fas and FasL single-nucleotide polymorphisms (SNPs) was observed between women with RPL and fertile controls among Korean women. To determine the possibility of genetic polymorphisms in Fas and its ligand as risk factors for RPL, further studies in various races and a large study population are needed.     

Haplotype analysis of TGF-β1 gene in a preeclamptic population of northern Mexico

ObjectiveTo determine the frequencies of −800G/A (rs1800468), −509C/T (rs1800469) and 869T/C (rs1800470) polymorphisms and their haplotypes in the TGF-β1 gene and their association with preeclampsia in a population of northern México.Design and methodsThis case-control study involved 175 preeclamptic and 253 normoevolutive pregnant women. The polymorphisms were genotyped by real time PCR.ResultsThe allele and genotype frequencies of polymorphisms showed no significant differences between cases and controls; the −800AA genotype had a very low frequency in cases (1%) and controls (0.4%). The TT genotype of the 869T/C polymorphism is a protective factor of severe preeclampsia (OR 0.56, 95% CI 0.32–0.98). The −509C/T and 869T/C polymorphisms were in linkage disequilibrium (D′ = .537, p = .009). The most common haplotypes in case and control groups were −800G/−509C/869C, 34.95% and 37.24%, respectively. We found no increased risk of preeclampsia by haplotype.ConclusionsOur results suggest that −800G/A, −509C/T and 869T/C polymorphisms of TGF-β1 gene or their haplotypes are not associated with preeclampsia and that only the TT genotype of 869T/C polymorphism is a protective factor of severe preeclampsia in a population of northern México.     

Association of vitamin D receptor gene polymorphism with bone mineral density in Slovenian postmenopausal women.

Osteoporosis is a common bone disease which affects one in three women after the 60th year of life and is a major cause of morbidity in older people. To identify patients with osteoporosis, measurement of bone mineral density (BMD) is recommended. The association of BMD with vitamin D receptor (VDR) genotype in Slovenian postmenopausal women was studied. We determined VDR genotype in 102 late postmenopausal women aged 47-77 years. BMD measurements were performed at the level of the lumbar spine (L2-L4) by dual X-ray absorptiometry. Our data show significantly lower BMD in BB women compared to those with bb genotype. The relative distribution of VDR genotypes and alleles in the Slovenian population was 18.6:57.8:23.6% for BB:Bb:bb, respectively. The results are consistent with those of a previous study which found an excellent correlation between BB VDR genotype and low BMD. The data were derived from a relatively small, but ethnically homogeneous population of the same socioeconomic status, with very similar dietary and physical activity habits. Dietary habits in particular seem to be important because of the relatively low calcium intake which may enhance the phenotypic expression of VDR gene polymorphisms.     

Preterm delivery and cytokine gene polymorphisms

OBJECTIVE: To investigate the association of preterm delivery with polymorphisms of IL-6, IL-10, IFN-gamma, TGFbeta1 and TNF-alpha genes. STUDY DESIGN: The study group consisted of 45 Caucasian, 81 mixed race and 13 black women with a history of preterm labor, consecutively referred. All of them had delivered before 37 weeks' gestation. The control group was composed of 56 Caucasian, 48 mixed race and 15 black women with successful pregnancy. DNA was extracted from whole blood, and cytokine genotyping was performed using the Cytokine Genotyping Tray (One-Lambda, Canoba Park, California). The polymorphisms analyzed were: TNF-alpha (-08 G --> A), IL-10 (-1082 G --> A), IL-6 (-174 G --> C), TGFbeta1 (+10 T --> C e 25 C --> G) and IFN-gamma (+874 A --> T). RESULTS: There were no differences in genotype frequencies of IL-10, TGF-beta, TNF-alpha or IL-6 polymorphisms between the groups. In the Caucasian group there was a trend toward increased frequencies of the TT genotype of IFN-gamma in controls. CONCLUSION: Preterm delivery is not associated with TNF-alpha (-308), IL-10 (-1082), IL-6 (-174), TGFbeta1 (+10 e 25) or IFN-gamma (+874) polymorphisms.     

Association study of IL-10 and IFN-gamma gene polymorphisms in Iranian women with preeclampsia

Preeclampsia (PE) is one of the most serious disorders of human pregnancy and Th1/Th2 imbalance may play a role in its etiology. Considering that cytokine production is under genetic control, in this study we have investigated IFN-gamma+874 (T/A) and three bi-allelic IL-10 promoter polymorphisms in a total of 134 preeclamptic women compared to 164 healthy women. It was shown that the IL-10 -1082 G allele frequency increases significantly in patients compared to the control group (P=0.045). No significant differences were found in any other genotype or allele frequencies of IL-10 and IFN-gamma genes between the two groups. In addition, the frequencies of three common IL-10 haplotypes (GCC, ACC, ATA) did not show any significant difference between the study groups. Since the presence of G nucleotide at position -1082 of IL-10 gene is associated with reduced cytokine production, therefore, the higher frequency of IL-10 -1082 G allele in preeclamptic patients compared to controls may be considered as a genetic susceptibility factor for the development of PE.     

VDR FokI polymorphism and its potential role in the pathogenesis of gestational diabetes mellitus and its complications

The aim of the study is evaluating the associations of FokI vitamin D receptor (VDR) gene polymorphisms with gestational diabetes mellitus (GDM), and its relations with postpartum metabolic syndrome. In a cohort study, 303 women referred to outpatient clinic of Shariati Hospital. The VDR FokI genotypes were determined. All subjects were followed 6–12 weeks after delivery. The frequencies of Ff, FF, and ff genotypes were 30.4% (49), 63.4% (102), and 6.2% (10), respectively, in healthy pregnancies and 34.5% (49), 54.9% (78), and 10.6% (15), respectively, in GDM patients. The ff genotype was more common in GDM patients. Healthy individuals had higher frequency of F allele, suggesting that F allele may have a role in decreased incidence of GDM. Concerning the GDM risk factors, f allele had significant association with prepregnancy obesity and family history of diabetes. In postpartum follow-up, women who developed metabolic syndrome were significantly older with higher prepregnancy body mass index, had more family history of diabetes, and also their ff genotype was two fold more frequent. Our results indicate a meaningful association between FokI VDR genotypes and an increase risk of GDM in Iranian population as well as its effects on postpartum metabolic syndrome.     

Promoter region polymorphisms in the transforming growth factor beta-1 (TGFβ1) gene and serum TGFβ1 concentration in preeclamptic and control Iranian women

Preeclampsia (PE) is a pregnancy associated disorder characterized by hypertension and proteinuria, which causes neonatal and maternal morbidity and mortality. The Th1/Th2 cytokine paradigm of the immune adaptation in pregnancy is now expanded to include Th1/Th2/Th17 and regulatory T (Treg) cells. Among cytokines, TGFβ1 has properties that justify evaluation of its role in PE etiopathology. In this investigation the polymorphisms of the TGFβ1 gene at promoter region, positions -800G→A and -509C→T, were studied in 142 PE and 140 normal pregnant female subjects using PCR-RFLP. Additionally, serum TGFβ1 was determined by ELISA. At position -800G→A genotypes and allele frequencies showed no significant differences between PE patients (GG 73.9%; GA 21.1%; AA 4.93%) and normal control (GG 70%; GA 28.6%; AA 1.4%) women. However the AA genotype at this position was more frequent in PE patients than in the control group. At -509C→T position, genotypes and allele frequencies showed no significant differences between PE patients and control individuals. The CC genotype at -509C→T position was more prevalent in PE patients than in the control group. The mean serum TGFβ1 level was significantly higher (62.14 ng/ml) in PE patients compared with pregnant and non-pregnant control groups (and 47.01 and 40.68 ng/ml, respectively). In conclusion, the promoter region polymorphisms of TGFβ1 may not be associated with PE, but serum levels of this cytokine may contribute to the etiopathology of PE.     

Polymorphism of the interleukin 1 receptor antagonist (IL1Ra) gene and placental abruption

Candidate genes with a possible involvement in placental abruption are mainly those related to thrombophilia and preeclampsia. Some reports have shown by placental histologic investigation that increased risk of placental abruption is associated with prolonged inflammation. The polymorphic allele A2 in the gene coding for interleukin 1 receptor antagonist (IL1Ra) has been associated in various diseases of autoimmune or inflammatory nature. In obstetrics, previous research data has linked altered IL1Ra protein production with placental pathology and some severe pregnancy complications. In this study, we have determined whether IL1Ra gene polymorphism is associated also with an increased risk of placental abruption. The study involved 116 women with placental abruption and 112 healthy control pregnant women who were genotyped for polymorphism of the IL1Ra gene. The genotype and allele frequencies were assessed between the two groups and also compared with those in the general population. The frequency of the A2 allele was 28.0% among cases and 33.0% in controls (p=0.29), both similar to that in the general population (28.9%). In addition, the genotype distribution of IL1Ra polymorphisms was similar in both groups. Interestingly, there were a relatively higher number of cases with allele A3 (n=4; 1.7%) compared with the controls (0.4%) and the general population (1.0%) but the difference was not statistically significant. We conclude that there is no significant difference in IL1Ra polymorphisms between patients with and without placental abruption.     

不良孕产史人群中血栓前状态易感基因分布调查

Objective?To explore the distribution of prethrombotic state susceptibility gene polymorphisms in the population with a history of poor pregnancy. Methods?From December 2018 to June 2021, 410 women with a history of poor pregnancy and childbirth (research group) and 111 normal women (control group) were collected as the research subjects. EDTA anticoagulated whole blood of the two groups were collected,its genomic DNA were extracted,fluorescence quantitative PCR technology was used to detect the distribution of prethrombotic state susceptibility gene polymorphisms. Results?① There was no significantly difference in MTHFR A1298 C, PAI-1 5G/4G, FⅤ A1691G, FⅡG20210A gene polymorphisms between the two group (P>0.05);② There were significantly difference in the distribution of genotypes in MTRR A66G sites AA,AG,GG between the two group (P<0.05).③ There were significantly difference in the AA,AG,GG genotypes and the G, A allele frequencies at the C677T site of MTHFR between the two group (P<0.05). Conclusion?The prethrombotic state susceptibility gene MTRR A66G locus and MTHFR C677T locus polymorphisms are related to the history of adverse pregnancy and childbirth.     

Interaction between the polymorphisms of the renin-angiotensin system in preeclampsia

Preeclampsia is considered to be a multifactorial and multisystemic disorder with a genetic predisposition. Alterations in the renin-angiotensin system are considered to play a significant role in the pathogenesis of the disease. In order to investigate the possible association of the three most common polymorphisms of the renin-angiotensin system genes with preeclampsia we have examined 41 women with preeclampsia and 102 normotensive pregnant women. DNA samples were genotyped for the M235T polymorphism of the angiotensinogen gene (AGT), the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme gene (ACE) and the A1166C polymorphism of the angiotensin II type 1 receptor gene (AT1R) by PCR. Allele and genotype frequencies of the AGT gene polymorphism differed between the two study groups. The TT genotype of the M235T polymorphism was significantly increased in women who developed preeclampsia (P<0.02). In addition, women with preeclampsia and TT genotype had more frequently the DD genotype or the 1166C allele than the control group showing a significant interaction between the genes. In conclusion, we found an association between the angiotensinogen variant 235T and preeclampsia as well as an interaction between the variant 235T and the two other genes studied.     

Interleukin-18 gene promoter polymorphisms and recurrent spontaneous abortion

BACKGROUND: IL-18 is a multifunctional cytokine capable of inducing either Th1 or Th2 polarization depending on the immunologic milieu. IL-18 is detected at the materno-fetal interface very soon in early pregnancy. Two polymorphisms in the promoter region of the IL-18 gene at positions of -607 and -137 appear to have functional impacts. OBJECTIVE: This study attempts to evaluate the frequency of these two polymorphisms in the IL-18 gene promoter in patients with recurrent spontaneous abortion (RSA) and normal pregnant women. SUBJECTS AND METHODS: One hundred and two RSA patients and 103 healthy pregnant women were enrolled in this study. Single nucleotide polymorphisms of the IL-18 gene at positions -607 (C/A) and -137 (G/C) were analyzed by the sequence-specific PCR method. RESULTS: There was no significant association between the allele, genotype, and haplotype frequencies of the two single nucleotide polymorphisms (SNPs) in the IL-18 gene promoter and RSA. CONCLUSION: The results of this study showed that IL-18 gene promoter polymorphisms at positions -607 and -137 did not confer susceptibility to RSA in southern Iranian patients.