The relationship of the ESR1 gene polymorphisms with the presence of coronary artery disease determined by coronary angiography

Effects of estrogen on the cardiovascular system, mediated mainly by estrogen receptor type alpha (ER alpha), have been well-defined and specific polymorphisms in the ER alpha gene (ESR1) have been associated with several coronary heart diseases including coronary artery disease (CAD) in studies covering different populations. In the present study, we aimed to investigate whether there is an association between two of the known polymorphisms in the ESR1, named c.454-397T>C and c.454-351A>G, and CAD in a Turkish population. One hundred sixty eight patients with CAD and 99 patients without CAD were included in the study. The ESR1 c.454-397T>C and c.454-351A>G polymorphisms were studied by the conventional polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. While no association was found between the c.454-351A>G polymorphism and CAD, the c.454-397T>C genotype distributions were statistically significant independent of known risk factors between CAD-positive (CAD+) and CAD-negative (CAD-) groups (p = 0.001). TT genotype was more frequent in CAD- group than in CAD+ group, 22.2% and 4.8%, respectively. CC genotype was associated with increased risk of CAD (p = 0.001) compared to the TT genotype. When comparing the distribution of CC + TC genotypes to that of TT genotype in CAD+ and CAD- groups, the frequency of CC + TC genotypes showed a significant increase independent of known CAD risk factors in CAD+ subjects (p = 0.001). As a conclusion, a statistically significant relationship between the ESR1 c.454-397T>C polymorphism and CAD were found independent of known CAD risk factors in a Turkish population.     

Transferase S-glutathione class pi gene (GSTP1) polymorphism in thyroid cancer patients

INTRODUCTION: One of the potential genes which can increase the risk of cancer is GSTP1 gene. It encodes enzyme called glutathione S-transferase pi class, which is involved in the detoxification of a variety of potential carcinogenic compounds. Polymorphism in this gene can cause the amino acid substitution. This substitution, close to the substrate binding site, changes the enzymatic activity for particular substrates and subsequently increases the risk of carcinogenesis. The aim of this study was to evaluate the function of GSTP1 polymorphism in thyroid cancer and possible association between GSTP1 polymorphism and age at diagnosis. MATERIAL AND METHODS: 103 patients with differentiated thyroid cancer (DTC) and 53 individuals from control group were examined using PCR-RFLP. RESULTS: Statistically insignificant association of studied polymorphisms with thyroid cancer was observed. Comparison of allele frequency between cases and control groups revealed the presence of risk alleles. For the first polymorphism Ile OR = 1.257; 95% CI [0.792-1.997] (p = 0.332), and for the second one Val OR = 1.283; 95% CI [0.6260-2.631] (p = 0.495). The presence of Val/Val (c.313A>G) led to a significant earlier age of onset as compared with other genotypes (p < 0.05). Mean age at diagnosis for Val/Val genotype was 41.1 +/- 15.2, and for Ile/Val + Ile/Ile reached 48.9 +/- 13.2. There was no association between age and genotype for c.341C>T polymorphism. CONCLUSIONS: Statistically insignificant association of GSTP1 gene polymorphism with thyroid cancer was observed in studied group of patients. The Val/Val genotype for c.313A>G polymorphism led to earlier age of tumour diagnosis as compared with other genotypes.     

Functional polymorphisms of cyclooxygenase-2 gene and risk for hepatocellular carcinoma

Cyclooxygenase-2 (COX-2) influences carcinogenesis through immune response suppression, apoptosis inhibition, regulation of angiogenesis and tumor cell invasion, and metastasis. It is now well established that COX-2 is overexpressed in many premalignant, malignant, and metastatic cancers, including hepatocellular carcinoma (HCC). DNA sequence variations in the COX-2 gene may lead to altered COX-2 production and/or activity, and so they cause inter-individual differences in the susceptibility to HCC. Functional coding region polymorphisms -1195A>G (rs689466), -765G>C (rs20417), and +8473T>C (rs5275) in the COX-2 gene have recently been shown to be associated with several human cancers but their association with HCC has yet to be investigated. We used hospital-based case-control study to assess the hypothesis that the functional COX-2 variation may affect individual susceptibility to the HCC. COX-2 polymorphisms were investigated in 129 confirmed subjects with HCC and 129 cancer-free control subjects matched on age, gender, smoking, and alcohol consumption using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The distribution of the COX-2 -1195A>G and +8473T>C genotypes were not significantly different between HCC cases and control. However, proportion of the COX-2 -765CC genotype which leads to a 30% reduction of the COX-2 promoter activity was significantly lower in patients with HCC (3.1%) when compared to control subjects (11.6%) (P < 0.05). Logistic regression analyses revealed that the COX-2 -765G>C variant genotype (-765CC) was associated with a significantly decreased risk of HCC compared with the -765GG wild-type homozygotes [P < 0.05, odds ratio (OR) = 0.25, 95% confidence interval (CI) = 0.08-0.79]. Our results suggest for the first time that the -765CC genotype of COX-2 -765G>C polymorphism, causing lower COX-2 gen expression, is a genetic protective factor for HCC. However, because this is the first report concerning the COX-2 -1195A>G, -765G>C, and +8473T>C polymorphisms and the risk of HCC, independent studies are needed to validate our findings.     

Polymorphisms of the TIM-1 gene are associated with rheumatoid arthritis in the Chinese Hui minority ethnic population

The T-cell immunoglobulin and mucin domain 1 (TIM-1) is known to be associated with susceptibility to rheumatoid arthritis (RA). We investigated the association of four single-nucleotide polymorphisms (SNPs) in the promoter region of the TIM-1 gene with susceptibility to RA in a Chinese Hui ethnic minority group. Using RFLP or sequence specific primer-PCR, 118 RA patients and 118 non-arthritis control individuals were analyzed for the -1637A>G, -1454G>A, -416G>C, and -232A>G SNPs in the TIM-1 gene. The polymorphisms -232A>G and -1637A>G in the promoter region of TIM-1 were found to be associated with susceptibility to the RA gene in the Hui population, while -416G>C and -1454G>A SNPs were not. Of these, the polymorphism of -232A>G is inconsistent with that found in a Korean population, suggesting that genetic variations of the TIM-1 gene contribute to RA susceptibility in different ways among different populations. Based on haplotype analysis, individuals with haplotypes AGCA (Χ(2) = 22.0, P < 0.01, OR (95%CI) >1), AGCG (Χ(2) = 18.16, P < 0.01, OR (95%CI) >1) and AGGA (Χ(2) = 5.58, P < 0.05, OR (95%CI) >1) are at risk to develop RA in the Chinese Hui population; those with the GAGA (Χ(2) = 7.44, P < 0.01, OR (95%CI) <1) haplotype may have a decreased likelihood of RA. GGCA and GGCG are more common in both RA and non-RA subjects. We conclude that -1637A>G and -232A>G polymorphisms of TIM-1 are associated with susceptibility to RA in the Chinese Hui population.     

Association of epidermal growth factor receptor (EGFR) gene polymorphism with lung cancer risk: a systematic review

Abstract

Epidermal growth factor receptor (EGFR) is a member of the tyrosine kinase receptor family, which is thought to be involved in the development of cancer, as the EGFR gene is often amplified, and/or mutated in cancer cells. Lung cancer remains one of the most major causes of morbidity and mortality worldwide, accounting for more deaths than any other cancer cause. Gene polymorphism factor has been reported to be an important factor which increases the susceptibility of lung cancer. There lacks a well-documented diagnostic approach for the lung cancer risk, and the etiology of lung cancer is not clear. The current systematic review was performed to explore the association of EGFR gene polymorphism with lung cancer risk. In this review, association of EGFR 181946C?>?T, 8227G?>?A gene polymorphism with lung cancer was found, and EGFR Short genotype of cytosine adenine repeat number polymorphism was significantly associated with an increased risk of lung cancer.     

Interferon gamma and Interleukin 10 polymorphisms in Brazilian patients with systemic lupus erythematosus

The pathogenesis of systemic lupus erythematosus (SLE) is complex, with several susceptibility genes and environmental factors involved in its development and clinical manifestation. Currently, there is a great amount of interest in the identification of biomarkers, as cytokines, that can quantify the susceptibility of SLE, the risk of future organ involvement, and association of their changes with disease activity. To investigate the associations between polymorphisms in the gene of Interferon gamma (IFN-γ) and in the promoter of the Interleukin-10 (IL-10) gene and SLE. The polymorphisms +874 T/A (rs2430561) in the IFN-γ gene and ?1082G/A (rs1800896) in the IL-10 promoter were determined in 99 SLE patients and 100 healthy controls among women Brazilian using the refractory mutation system polymerase chain reaction method. Disease activity was assessed using the SLE activity index. There were significant differences in the distribution of the genotype T/A in IFN-γ gene polymorphism (+874) (χ ² = 7.168; P = 0.0074) and the genotype G/A in IL-10 promoter polymorphism (?1082) (χ ² = 4.654; P = 0.0310) between the SLE and control groups. However, no association was observed between clinical features and the polymorphisms studied. This study presents preliminary evidence for association between IL-10 and IFN-γ polymorphism and SLE susceptibility, but not with clinical features in a Northeast population from Brazil.     

The MHC2TA -168A>G gene polymorphism is not associated with rheumatoid arthritis in Austrian patients

An association between susceptibility to rheumatoid arthritis (RA) and a common -168A>G polymorphism in the MHC2TA gene with differential major histocompatibility complex (MHC) II molecule expression was recently reported in a Swedish population. The objective of the present study was to replicate this finding by examining the -168A>G polymorphism in an Austrian case-control study. Three hundred and sixty-two unrelated RA cases and 351 sex-matched and age-matched controls as well as 1,709 Austrian healthy individuals were genotyped. All participants were from the same ethnic background. Genotyping was performed using 5' allelic discrimination assays. The association between susceptibility to RA and the -168A>G single nucleotide polymorphism was examined by chi-square test. Comparison was made assuming a dominant effect (AG + GG genotypes versus AA genotype). In contrast to the primary report, the frequency of MHC2TA -168G allele carriers was not significantly different between patients and controls in the Austrian cohort. The homozygous MHC2TA -168 GG genotype was more frequent in matched controls than in Austrian RA patients. There was no association between the presence of RA-specific autoantibodies and the MHC2TA -168 GG genotype. In this cohort of Austrian patients, no association between the MHC2TA polymorphism and RA was found.     

Prostate-specific antigen and 17-hydroxylase polymorphic genotypes in patients with prostate cancer and benign prostatic hyperplasia

We investigated the association of prostate cancer (PCa) and benign prostatic hyperplasia (BPH) with genetic polymorphisms in prostate-specific antigen (PSA) (-158 G/A) and 17-hydroxylase (CYP17) (-34 T/C) genes in a Turkish population. In this study, we investigated the distribution of these polymorphisms in 148 PCa patients, 136 BPH patients, and 102 healthy individuals as controls. The polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism assay. Genotype and allele frequencies were calculated, and their associations with PCa or BPH risk are assayed. The frequency of PSA gene GA and GG genotypes was significantly higher in PCa patients than in controls (p = 0.017 and p = 0.019, respectively). GG genotype was also associated with BPH (p = 0.033). In a case analysis, according to Gleason score, the association of PSA gene GG genotype with Gleason score >7 was near to statistical significance (odds ratio, 2.94; 95% confidence interval, 0.95-9.28). There was also an association between CYP17 polymorphism and BPH (p = 0.004). No association was observed between PCa and CYP17 gene polymorphism. These data demonstrate that PSA gene promoter variation may play a significant role in the development of PCa and BPH, and that CYP17 gene polymorphism may be associated with BPH in the Turkish population studied.     

The HHEX rs1111875A/G gene polymorphism is associated with susceptibility to type 2 diabetes in the iranian population

The illuminating picture of genetic mechanisms underlying the development of type 2 diabetes (T2DM) includes differently accumulated genetic polymorphisms that increase the risk along with environmental factors. A number of single nucleotide polymorphisms (SNPs) are indicated to be linked with T2DM, but also conflicting results have been found. To examine the contribution of these polymorphisms in conferring susceptibility to T2DM, the association of HHEX rs1111875A/G and CDKN2A/B rs10811661C/T common gene polymorphisms with the risk of T2DM in an Iranian population was evaluated. In this study participated 140 patients and 140 controls. Genomic DNA was extracted from samples and genotyping of the polymorphisms was performed by the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) technique. A significant association was found with the G allele (OR = 1.729, CI = 1.184–2.523, P = 0.004) and GG genotype (OR = 2.921, 95% CI = 1.789–4.771, P< 0.001) of the rs1111875A/G SNP for susceptibility to T2DM in the recessive model. Furthermore, compared with the GG genotype, individuals with the GA genotype had a lower risk to develop T2DM (OR = 0.237, 95% CI = 0.137–0.408, P< 0.001) in the additive model. In addition, an association between the polymorphism and BMI in regard to the risk of T2DM was identified. The genotype and allele frequencies of the rs10811661C/T polymorphism did not show a statistically significant association with T2DM in any genetic model. Our results show that the rs1111875A/G polymorphism is an important susceptibility polymorphism for the development of T2DM in the Iranian population. Also, these findings support that this polymorphism is a key genetic risk factor for the development of T2DM in multiple ethnic populations.

     

Association of IL1β and IL4 gene polymorphisms with nasal polyps in a Polish population

Imbalance between proinflammatory and anti-inflammatory cytokines may regulate the inflammatory reaction in the nasal polyps. Polymorphisms in the regulatory regions of the cytokines genes may influence their expression. The aim of this study was to investigate the relationship between an IL-1β and IL-4 promoter polymorphisms and nasal polyps. The C-511T promoter polymorphism of the IL-1β gene and C-590T promoter polymorphism of the IL-4 gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis in 208 Polish patients with nasal polyps and 200 healthy Polish subjects. The risk of susceptibility to NP was significantly higher in patients with NP who had ?511 T/T genotype of IL1β than in controls (OR 3.07; 95 % CI 1.18–7.99). No statistically significant differences were found between NP patients and the control group with regard to genotype distribution and allele frequencies of C/T polymorphism of IL4 gene. Our study demonstrated that the TT genotype for C-511T mutation associated with the risk of developing NP in a Polish population.     

Effects of rs769217 and rs1001179 polymorphisms of catalase gene on blood catalase, carbohydrate and lipid biomarkers in diabetes mellitus

Abstract Oxidative stress and deficiency of the enzyme catalase, which is the primary scavenger of the oxidant H(2)O(2), may contribute to diabetes. The current study examined two polymorphisms in the catalase gene, -262C>nT in the promoter and 111C>T in exon 9, and their effects on blood catalase activity as well as on concentrations of blood glucose, haemoglobin A1c, triglyceride, cholesterol, HDL, LDL, ApoA-I and ApoB. Subjects were type-1 and type-2 diabetics. We evaluated PCR-single strand conformational polymorphism for 111C>T and PCR-restriction fragment length polymorphism for -?262C>T. TT genotype frequency of 111C>T polymorphism was increased in type-1 diabetes. Type-2 diabetics with the CC or CT genotypes had decreased catalase and increased glucose, hemoglobinA1c and ApoB. Type-2 diabetics who have TT genotype in -262C>T may have elevated risk for diabetes complications; these patients had the lowest mean catalase and HDL, as well as the highest glucose, haemoglobin A1c, cholesterol and ApoB.     

Cytokine gene polymorphisms and susceptibility to cutaneous leishmaniasis in Iranian patients

Cutaneous Leishmaniasis (CL) is one of the most prevalent clinical forms of leishmaniasis. Preliminary data suggest that cytokine gene polymorphisms can contribute to resistance or susceptibility to CL. Therefore, we investigated the association of functional polymorphisms in four cytokine genes with susceptibility to, and clinical outcome of CL. A total of 201 patients with self-healing cutaneous leishmaniasis (SCL) and 92 asymptomatic infected controls (AIC) from Fars province as well as 58 patients with chronic cutaneous leishmaniasis (CCL) and their 688 normal controls (normal Iranian population or NIP) who were collected from the different areas of Iran were included in the study. The allele-specific oligonucleotide polymerase chain reaction (ASO-PCR) or PCR-RFLP (restriction fragment length polymorphism) methods were used for genotyping. The frequency of TNF-alpha -308 G-->A and TNF-beta +252 G-->A gene polymorphisms were not different between studied groups. Distribution of IFN-gamma +874 A-->T and IL-4 -590 C-->T polymorphism were also compared between SCl or CCL patients and their controls. IFN-gamma +874 A-->T polymorphism was less common in CCL patients compared to the NIP (chi(2)=12.53, p=0.0019). Significant differences in frequency of IL-4 -590 C -->T polymorphism were also found between the SCL and AIC (chi(2)=8.64, p=0.003). In conclusion, our results suggest that functional genetic variants in the IL-4 promoter could influence the risk of developing CL while the polymorphism in the first intron of the IFN-gamma gene might influence the progression of disease towards CCL.     

miR-30a promoter variation contributes to the increased risk of colorectal cancer in an Iranian population

Cytochrome P450 family 24 subfamily A member 1 (CYP24A1) gene is overexpressed in many cancers including colorectal cancer (CRC) and correlated with tumor invasion, lymph node metastasis, and the reduced overall survival. We predicted that miR-30a and miR-125a regulate the CYp24A1 gene expression. Therefore, we performed a case-control study using 800 individuals, including 389 patients with CRC and 411 noncancer controls to evaluate the association between miR-30a rs2222722 and miR-125a rs12976445 polymorphisms, located at in the promoter region, and the risk of sporadic CRC in an Iranian population. The genotyping assay for both polymorphisms was performed using Tetra-primer amplification refractory mutation systems polymerase chain reaction. The results indicated that the frequency of the miR-30a rs2222722 CT genotype was significantly different in the studied groups ( P = 0.0001; odds ratio [OR] = 1.9; 95% confidence interval [CI], 1.39-2.60). Also, a significant difference was observed under the dominant inheritance model ( P = 0.0001; OR = 1.8; 95% CI, 1.33-2.43). The frequency of the miR-30a rs2222722 T allele was significantly associated with increased CRC risk in the studied population ( P = 0.0019; OR = 1.47; 95% CI, 1.15-1.89). Taken together, our study provides preliminary evidence that the rs2222722 polymorphism increases the susceptibility to CRC in an Iranian population. Therefore, the affecting factors on CYP24A1 gene expression such as microRNAs can be considered as risk factors for CRC.     

Extended haplotype analysis of ovine ADRB3 using polymerase chain reaction single strand conformational polymorphism on two regions of the gene

The β3 adrenergic receptor (ADRB3) plays a critical role in the regulation of energy metabolism in mammals. In sheep, intronic polymorphism of the ADRB3 gene has been associated with lamb survival and various production traits. This study investigates variation in the ovine ADRB3 3' untranslated region (3'UTR), a region that may impact expression of the gene. Using PCR- single strand conformational polymorphism (SSCP), six unique patterns (named a-f) were observed in an approximately 304-bp amplicon. Sequencing revealed three single-nucleotide polymorphisms (c.*233A>C, c.*271G>C, c.*357A>T) and a single-nucleotide deletion (c.*257delG). Haplotype analyses showed that the previously described allele A defined by variation in the ovine ADRB3 intron can be divided into three haplotypes (Aa, Ab, and Ac). In total, 16 haplotypes through ovine ADRB3 were detected. This study suggests that ovine ADRB3 is highly polymorphic and that the extended haplotype analysis through the promoter, 5'UTR, coding sequence, intron, and 3'UTR needs to be performed to define the full extent of variation in this gene.     

延边朝鲜族和汉族脂联素启动子SNPs与原发性高血压的相关性

为了探讨延边朝鲜族和汉族脂联素基因启动子单核苷酸多态性(SNPs)与原发性高血压(EH)的关系, 文章采用PCR产物直接测序方法检测了220例EH患者和268例对照个体的脂联素启动子5个SNPs位点: -11426A>G(rs16861194)、-11391G>A(rs17300539)、-11377C>G(rs62620185)、-11156insCA(rs60806105)、-11043C>T(rs76786086), 氧化酶法测定空腹血糖、甘油三酯、总胆固醇、低密度脂蛋白、高密度脂蛋白, 酶联免疫吸附法(ELISA)测定血浆脂联素和胰岛素。结果显示: (1) -11426A>G、-11377C>G 和-11156insCA 3个位点具有多态性, 且它们的基因型频率分布符合Hardy-Weinberg平衡定律(P>0.05), -11391G>A和-11043C>T位点无多态性; (2) -11426A>G和-11156insCA呈完全连锁不平衡(D’=1; r2=1); (3) -11426G基因频率比较, 朝鲜族(21.10%)高于汉族(12.05%), 汉族EH组高于对照组; -11377C>G的基因型和基因频率在朝鲜族和汉族间及同一民族内EH组和对照组间比较均无统计学意义(P>0.05); (4)单倍型?11426G -11377C的频率, 汉族EH组高于对照组(P<0.05), 朝鲜族EH组和对照组比较无统计学意义(P>0.05); (5)EH组的血浆脂联素水平明显低于对照组(P<0.001)。据此得出结论: (1)首次发现?11426A>G和?11156insCA呈完全连锁不平衡, -11426 A>G的多态性在朝鲜族和汉族中存在民族差异; (2) -11426 G和-11426G -11377C是延边汉族EH的危险因子和危险单倍型, 但不是朝鲜族的; (3)低血浆脂联素是延边朝鲜族和汉族EH的重要危险因素; (4)血浆脂联素水平与-11426A>G基因型无关。     

Interleukin-10 gene promoter polymorphisms and their protein production in pleural fluid in patients with tuberculosis

Associations of interleukin-10 (IL-10) gene promoter polymorphisms and pleural tuberculosis risk remain unclear. The objective of this study was to determine IL-10 gene promoter polymorphisms at -1082, -819 and -592 sites and their protein production in pleural fluid (PF) in patients with and without pleural tuberculosis. IL-10 gene promoter polymorphisms at the -1082, -819 and -592 sites were genotyped using a SNaPshot assay. Protein levels of IL-10 in PF were measured using an enzyme-linked immunosorbent assay. There were no significant differences in the genotype and allele frequencies of IL-10 gene promoter polymorphisms at position -1082 between the pleural tuberculosis and the control groups. However, the frequency of -819 T or -592 A alleles was significantly more common in patients with pleural tuberculosis than controls. The protein levels of IL-10 in PF were statistically higher in the pleural tuberculosis group than in the control group. Moreover, the polymorphisms at the -1082, -819 and -592 sites were associated with protein levels of IL-10 in PF in the pleural tuberculosis group, while in the control group, only the polymorphism at position -1082 correlated with the protein levels. These findings support the association between IL-10 promoter polymorphisms at -819 and -592 sites and their protein production with pleural tuberculosis risk.