Simultaneous identification of GSTP1 Ile105→Val105 and Ala114→Val114 substitutions using an amplification refractory mutation systempolymerase chain reactionassay: studies in patients with asthma

Background  

The glutathione S-transferase (GST) enzyme GSTP1 utilizes byproducts of oxidative stress. We previously showed that alleles of GSTP1 that encode the Ile105→Val105 substitution are associated with the asthma phenotypes of atopy and bronchial hyperresponsiveness (BHR). However, a further polymorphic site (Ala114→Val114) has been identified that results in the following alleles: GSTP1 ^* A (wild-type Ile105→Ala114), GSTP1 ^* B (Val105→Ala114), GSTP1 ^* C (Val105→Val114) and GSTP1 ^* D (Ile105→Val114).     

Analysis of the glutathione S-transferase P1 gene Ile105Val polymorphism in the patients with sporadic motor neuron disease from Russia

Ile105Val polymorphism in exon 5 of glutathione S-transferase (GSTP1) gene was examined in a group of patients with motor neuron disease (MND) and control sample. No statistically significant differences in the allele and genotype frequency distributions between the samples examined were demonstrated. We conclude that Ile105Val polymorphism is not associated with the risk of the disease development in the patients from Russia with sporadic form of MND.     

GSTP1 Ile105Val polymorphism is associated with lung cancer risk among Asian population and smokers: An updated meta-analysis

Many studies have examined the association between the GSTP1 Ile105Val (rs 1695) gene polymorphism and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The PubMed and CNKI database was searched for case–control studies published up to July 2012. Data were extracted and pooled odds ratios (OR) with 95 % confidence intervals (CI) were calculated. Ultimately, 42 studies, comprising 12,304 lung cancer cases and 15,729 controls were included. Overall, for G allele carriers (GA + GG) versus homozygote AA, the pooled OR was 1.05 (95 % CI 0.99–1.10 P = 0.092 for heterogeneity), for GG versus AA the pooled OR was 1.04 (95 % CI 0.96–1.12 P = 0.084 for heterogeneity). In the stratified analysis by ethnicity, gender, histological types of lung cancer and smoking status, a significant association was found in Asians and smokers, not in Caucasian or mixed population, Male, Female population, lung AC, SCC, SCLC or non-smokers. Publication bias was found by using the funnel plot and Egger’s test. Overall, there is no evidence showing a significant correlation between GSTP1 Ile105Val gene polymorphism and lung cancer risk in overall population, however stratified analysis by ethnicity, histology, gender and smoking status, it correlate with increased lung cancer susceptibility among Asians and smokers.     

HER2 Ile655Val and PTEN IVS4 polymorphisms in patients with breast cancer

Although HER2/PTEN pathway is commonly disrupted in cancer, association of HER2 and PTEN polymorphisms with breast cancer (BC) remains controversial. We investigated the HER2 Ile655 Val and PTEN IVS4 polymorphisms in patients with BC in Turkish population. HER2 Ile655Val (rs 1136201) and PTEN IVS4 (rs 3830675) polymorphisms were determined using polymerase chain reaction-based restriction fragment length polymorphism (PCR–RFLP) in blood samples of 118 BC patients and 118 age-matched healthy controls. We found that the frequency of the Ile/Val genotype of HER2 Ile655Val gene was significantly higher in BC patients (p < 0.009; OR: 1,983 95 % CI: 1.181—3.328). The presence of ATCTT insertion (+/+) genotype at downstream of exon 4 in intron 4 of PTEN IVS4 gene was also associated with 1.83 fold decreased risk of BC development (p < 0.033; OR: 1.83, 95 % CI: 1.11—3.03). Analysis on clinico-pathological parameters showed neither HER2 Ile655Val nor PTEN IVS4 genotypes were not associated with any of the variables (p > 0.05).In conclusion, our findings suggest that the Ile/Val genotype of HER2 and ATCTT insertion (+/+) genotype of PTEN IVS4 gene may play an important role as genetic markers for breast cancer risk, but both genes genotypes may not be useful for predicting tumor prognosis in Turkish population.     

Effect of point substitutions in the MnSOD, GPX1, and GSTP1 genes on the risk of familial and sporadic breast cancers in residents of the Altaĭ region of the Russian Federation

The frequencies of the polymorphic gene variants MnSOD Ala9Val, GPX1 Pro198Leu, and GSTP1 Ile105 Val were estimated in female residents of Altai krai with breast cancer. The frequency distributions of the genotypes for all genes studied in both patients and control subjects fit the Hardy-Weinberg equilibrium. The estimated frequencies of the genotypes for the studied genes in the control group did not differ from those earlier reported for Caucasoid women living in Europe. The T(rs1050450) allele of the GPX1 gene was demonstrated to protect against sporadic breast cancer (OR = 0.74 (95% CI = 0.58-0.94), p = 0.012). Carriers of the genotype combination MnSOD CC + GPX1 CC were found to have a 1.6 times higher risk of sporadic breast cancer compared to the control group (OR = 1.59 (1.05-2.41), p = 0.0258). The polymorphic loci GSTP1 (rs1695) and MnSOD (rs4880) were not found to be significantly associated with the risk of familial or sporadic breast cancer.     

Associations between C1431T and Pro12Ala variants of PPARγ gene and their haplotypes with susceptibility to metabolic syndrome in an Iranian population

Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear hormone receptor that regulates a number of genes involved in lipid and carbohydrate metabolism. The aim of this study was to investigate the association of C1431T and Pro12Ala polymorphisms of PPARγ gene and their haplotypes and diplotypes with risk of metabolic syndrome (MetS) in an Iranian population. A total of 340 unrelated Iranian subjects, including 175 MetS patients and 165 normal controls were enrolled. Each group was then divided into two subgroups according to the genotype (Pro/Pro and Pro/Ala + Ala/Ala for Pro12Ala, CC and CT + TT for C1431T). Genotypes were determined using a TaqMan method. Anthropometric indices, fasting plasma glucose and fasting lipid profile were measured by routine methods. A significant difference in the frequencies of the C1431T genotypes was observed between MetS and control subjects (P = 0.014), whereas no association was found for the Pro12Ala. The T allele carriers had a significantly increased risk of MetS compared to the CC genotype (P = 0.016) even after correction for multiple-testing and adjustment for age, sex and genotype. The T allele may therefore be considered as a risk factor for MetS (P = 0.003). Analysis of combined groups showed that X/Ala-CC and Pro/Pro-X/T diplotypes were associated with a higher body weight, waist circumference and waist to hip ratio among the individuals with MetS. Moreover the Ala-T haplotype was weakly associated with a higher level of triglyceride and lower level of HDL, suggesting the possibility of an interaction between Ala and T alleles. This study suggests that the PPARγ C1431T polymorphism is related to an increased risk of MetS in an Iranian population and interacts with the Pro12Ala polymorphism, further increasing the risk of MetS.     

Association Between Apolipoprotein E Gene Polymorphism and Myocardial Infarction

We investigated apolipoprotein E (APOE) genotypic influence on myocardial infarction risk in South India, where the disease is emerging as a major threat to the public health care system. The study included 412 subjects: 202 myocardial infarction patients and 210 age- and sex-matched controls. DNA was isolated, the polymorphism of the APOE gene was subjected to PCR, and lipid levels were evaluated. The prevalence of E3/E4 genotypes in patients (18.3%) was 1.5-fold that of controls (11.0%, p < 0.05), and the prevalence of E2/E3 genotypes was higher in controls (6.7%) than in patients (4%). The ε4 allele was significantly associated with myocardial infarction: χ ² = 12.4; OR 2.2 (CI 95%: 1.4–3.4), p < 0.004, for ε4 versus ε3 and χ ² = 5.7; OR 2.7 (CI 95%: 1.1–6.5), p > 0.01, for ε4 versus ε2. A significant association of the ε4 allele, especially the E3/E4 genotype, with myocardial infarction was observed.     

Peroxisome proliferator-activated receptors alpha and gamma2 polymorphisms in nonalcoholic fatty liver disease: A study in Brazilian patients

Background

Non-alcoholic fatty liver disease (NAFLD) refers to the accumulation of hepatic steatosis in the absence of excess alcohol consumption. The pathogenesis of fatty liver disease and steatohepatitis (NASH) is not fully elucidated, but the common association with visceral obesity, hyperlipidemia, hypertension and type 2 diabetes mellitus (T2DM) suggests that it is the hepatic manifestation of metabolic syndrome. Peroxisome proliferator-activated receptor PPARα and PPARγ are members of a family of nuclear receptors involved in the metabolism of lipids and carbohydrates, adipogenesis and sensitivity to insulin. The objective of this study was to analyze the polymorphisms Leu162Val of PPARα and Pro12Ala of PPARγ as genetic risk factors for the development and progression of NAFLD.

Methods

One hundred and three NAFLD patients (89 NASH, 14 pure steatosis) and 103 healthy volunteers were included. Single nucleotide polymorphisms (SNPs) Leu162Val and Pro12Ala were analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP).

Results

NASH patients presented higher BMI, AST and prevalence of T2DM than patients with pure steatosis. A higher prevalence of 12Ala allele was observed in the NASH Subgroup when compared to Control Group. When we grouped NASH and Steatosis Subgroups (NAFLD), we found lower serum glucose and more advanced fibrosis in the Leu162Val SNP. On the other hand, there was no statistical difference in clinical, laboratorial and histological parameters according to the Pro12Ala SNP.

Conclusions

We documented a lower prevalence of 12Ala allele of gene PPARγ in the NASH Subgroup when compared to Control Group. In NAFLD patients, there were no associations among the occurrence of Pro12Ala SNP with clinical, laboratorial and histological parameters. We also documented more advanced fibrosis in the Leu162Val SNP. The obtained data suggest that Pro12Ala SNP may result in protection against liver injury and that Leu162Val SNP may be involved in the progression of NAFLD.     

Allelic variants of glutathione S-transferase P1-1 differentially mediate the peroxidase function of peroxiredoxin VI and alter membrane lipid peroxidation

The dual-functioning antioxidant enzyme peroxiredoxin VI (Prdx6) detoxifies lipid peroxides particularly in biological membranes, and its peroxidase function is activated by glutathione S-transferase Pi (GSTP). The GSTP gene is polymorphic in humans, with the wild-type GSTP1-1 A (Ile105, Ala114) and three variants: GSTP1-1B (Ile105Val, Ala114), GSTP1-1C (Ile105Val, Ala114Val), and GSTP1-1D (Ile105, Ala114Val). The focus of this study was to determine the influence of these polymorphisms on Prdx6 peroxidase function. Using extracellular generation of OH radicals and fluorescence (DPPP dye) detection, we found a fast (∼300 s) onset of lipid peroxidation in membranes of MCF-7 cells transfected with a catalytically inactive Y7F mutant of GSTP1-1 and either GSTP1-1B or GSTP1-1D. However, this effect was not detected in cells expressing either GSTP1-1A or GSTP1-1C. Imaging of DPPP-labeled MCF-7 cells showed fluorescence localized in the plasma membrane, but intensity was substantially diminished in the GSTP1-1 A- and GSTP1-1C-expressing cells. Moreover, in the Y7F mutant of GSTP1-1 A-, GSTP1-1B-, and GST1-1D-expressing cells OH generation resulted (after 36 h) in plasma membrane-permeability-related cell death, whereas GSTP1-1A- and GSTP1-1C-expressing cells had significantly better survival. We used FRET analyses to measure in vitro binding of purified GSTP1-1 allelic variant proteins to purified recombinant Prdx6. The affinities for Prdx6 binding to GSH-loaded GSTP1-1's either mirrored their observed peroxidase activities (using phospholipid hydroperoxide as a substrate), GSTP1-1A>GSTP1-1C (K_D=51.0 vs 57.0 nM), or corresponded to inactivation, GSTP1-1B (GSTP1-1D) (K_D=101.0 (94.0) nM). In silico modeling of the GSTP1-1–Prdx6 heterodimer revealed that the sites of GSTP1-1 polymorphism (Ile105 and Ala114) are in close proximity to the binding interface. Thus, there is a hierarchy of effectiveness for polymorphic variants of GSTP1-1 to regulate Prdx6 peroxidase function, a feature that may influence human population susceptibilities to oxidant stress.     

Genetic Polymorphisms and the Risk of Myocardial Infarction in Patients Under 45 Years of Age

This study investigates the potential role of 17 chosen polymorphisms in 15 candidate genes and the risk of myocardial infarction in patients under 45 years of age. The study consists of 271 patients with myocardial infarction and 141 controls. The analysis of genetic polymorphisms was performed using the PCR–RFLP method. Of the chosen polymorphisms, two (Leu125Val PECAM1 and A1/A2 FVII) are related to myocardial infarction and two (C677T MTHFR and 5A/6A MMP3) to advanced stenosis in arterial vessels (> 75%). We also found that the frequency of some combinations among the analyzed genes and environmental factors varied between the patient and control groups.     

Analysis of mitochondrial targeting sequence and coding region polymorphisms of the manganese superoxide dismutase gene in German Parkinson disease patients

Two polymorphisms of the MnSOD gene, Ile58Thr and Ala9Val, have been associated with Parkinson disease (PD). The Ile58Thr amino acid exchange affects the stability at the tetrameric interface of the enzyme and reduces the enzymatic activity of MnSOD while the Ala/Val substitution at position -9 of the mitochondrial targeting sequence (MTS) may lead to misdirected intracellular trafficking. We have analyzed 63 German Caucasian PD patients for possible sequence variation in the MTS as well as in exon 3 of the MnSOD gene. All 63 PD patients analyzed exhibited a T at nucleotide position 5777 in exon 3 of the MnSOD gene corresponding to ATA, or Ile at the peptide level, and no other sequence variants were found. In addition, both alleles of the Ala9Val polymorphism in the MTS of MnSOD were equally distributed between German PD patients and controls excluding this gene variant as a risk factor for PD in Caucasian subjects.     

XPC Lys939Gln and Ala499Val polymorphisms in colorectal cancer susceptibility: a meta-analysis of case–control studies

The XPC Lys939Gln and Ala499Val polymorphisms were likely to be involved with the development of colorectal cancer. However, there had been inconsistent reports of association. This meta-analysis of literatures was performed to draw a more precise estimation of the relationship. We systematically searched PubMed, Embase and Web of Science for relevant articles with a time limit of December 2012. The strength of association between the XPC Lys939Gln and Ala499Val polymorphisms and colorectal cancer susceptibility were assessed by odds ratio (OR) with the corresponding 95 % confidence interval (95 % CI). This meta-analysis including six case–control studies evaluated the associations between the two XPC polymorphisms (Lys939Gln, Ala499Val) and colorectal cancer susceptibility. For XPC Lys939Gln, no obvious associations were found for all genetic models [CC vs AA: OR (95 % CI) = 1.12 (0.94–1.32); CA vs AA: OR (95 % CI) = 1.08 (0.94–1.24); the dominant model: OR (95 % CI) = 1.09 (0.97–1.23); the recessive model: OR (95 % CI) = 1.07 (0.92–1.25)]. For XPC Ala499Val, no obvious associations were also not found for all genetic models [TT vs CC: OR (95 % CI) = 0.84 (0.65–1.10); CT vs CC: OR (95 % CI) = 1.00 (0.86–1.15); the dominant model: OR (95 % CI) = 0.98 (0.85–1.12); the recessive model: OR (95 % CI) = 0.87 (0.67–1.12)]. This meta-analysis suggested that both the XPC Lys939Gln and Ala499Val polymorphisms were not risk factors for increasing colorectal cancer.     

Val17Ile single nucleotide polymorphisms similarly as Ala15Thr could be related to the lower secretory dynamics of PAI-1 secretion: theoretical evidence

Plasminogen activator inhibitor (PAI-1) is a fast acting inhibitor of tissue and urokinase plasminogen activators (tPA and uPA). In that way PAI-1 regulates proteolytic activity of many physiological and pathological processes [1-3]. PAI-1 plays an important role in blood coagulation controlling clot lysis which is triggered by tPA activated plasminogen [4]. Only two types of mutations are reported to be associated with PAI-1; one is the frame-shift mutation in exon 4 of PAI-1 gene resulting in a truncated nonfunctional protein and in complete PAI-1 deficiency. The other SNP causes Ala15Thr mutation in the signal peptide. A literature search revealed five variants of polymorphisms during a study of over one thousand individuals. Two are associated with thrombophilia (765 4G/5G and -844 A>G, in the promoter), risk of myocardial infarction and postoperative deep venous thrombosis related to higher than normal levels of PAI-1. The other SNPs associated with PAI-1 deficiency are Ala15Thr, Val17Ile and they are located in the central hydrophobic core of the PAI-1 signal peptide of PAI-1 and Asn195Ile in the 'A' β sheet of the PAI-1. We have analyzed two SNPs not reported to be associated with PAI-1 deficiency. Our analysis suggests that Val17Ile PAI-1 variant might cause slower PAI-1 secretion leading to the deficiency at time and place where it is needed in a similar way as for Ala15Thr SNP. The Asn195Ile mutant may be more stable only as latent form thus no PAI-1 deficiency is expected in this mutant.     

VEGF and IL-4 gene variability and its association with the risk of coronary heart disease in north Indian population

Vascular endothelial growth factor (VEGF) is a potent angiogenic growth factor that has been shown to play a significant role in neovascularization during inflammation in atherosclerotic plaques, formation of collateral vessels to an area of ischemic myocardium and neovascularization at the edges of a myocardial infarction during its repair. Interleukin-4 (IL-4) has important role in immune cell chemotaxis, formation of endothelial cell adhesion molecules and has numerous anti-inflammatory effects which prevent the complications of atherosclerosis, the primary cause of coronary heart disease (CHD). In this study, we have analyzed the effect of 1154 A/G polymorphism of VEGF and 70 bp VNTR polymorphism of intron 3 in IL-4 genes in coronary heart disease (CHD) patients (n = 300) and their age matched controls (n = 300). To analyze polymorphic alleles, ARMS-PCR and RFLP techniques were used. Multiple logistic regression analysis was carried out with statistical software. GG genotype was associated with a decreased risk of development of CHD (OR 0.22, 95% CI 0.12–0.38, P < 0.001). However, A allele showed an increased risk whereas G allele decreased the risk of CHD with diabetes mellitus, hypertension, chronic mental stress and positive familial history of myocardial infarction (MI)/CHD. GG genotype was found to have protective effect with alcohol intake (OR 0.34, 95% CI 0.14–0.82, P < 0.01) and central obesity (OR 0.15, 95% CI 0.04–0.56, P < 0.001). GG genotype of VEGF has also shown significant association with IL-4 (P2P2 and P1P2) genotypes.     

Distribution of polymorphic variants of the <Emphasis Type="Italic">GSTP1</Emphasis> gene involved in biotransformation of xenobiotics in Tundra Nenets and Nganasans in comparison to Russians

The first study on the frequencies of polymorphic variants of the GSTP1 gene encoding glutathione-S-transferase P1 in Tundra Nenets and Nganasan populations was performed. The subject of the study was the single nucleotide polymorphisms rs1695 (Ile105Val substitution in the protein sequence) and rs1138272 (Ala114Val substitution) that had previously been shown to be associated with cancer and other multifactorial diseases. The data for Tundra Nenets of the Yamalo-Nenets autonomous okrug, Nganasans of the Taimyr Peninsula, and Russian residents of the Northern Siberia were compared. The frequencies of the mutant 105Val and 114Val variants were 10.8% and 0.8% in Nganasans, 23.7% and 4.8% in Nenets, and 35.8% and 9.1% in Russian population samples, respectively. The differences within all pairs of populations were significant for each allele. These differences may characterize the population-level susceptibility to cancer and other multifactorial diseases.     

Lifestyle factors modify obesity risk linked to PPARG2 and FTO variants in an elderly population: a cross-sectional analysis in the SUN Project

Genetic factors may interact with lifestyle factors to modify obesity risk. FTO and PPARG2 are relevant obesogenes. Our aim was to explore the effect of Pro12Ala (rs1801282) of PPARG2 and rs9939609 of FTO on obesity risk and to examine their interaction with lifestyle factors in an elderly population. Subjects (n = 978; aged 69 ± 6) were recruited from the SUN (Seguimiento Universidad de Navarra) Project. DNA was obtained from saliva, and lifestyle and dietary data were collected by validated self-reported questionnaires. Genotyping was assessed by RT-PCR plus allele discrimination. Subjects carrying the Ala allele of PPARG2 gene had a significantly increased obesity risk compared to non-carrier (Pro12Pro) subjects (OR, 1.66; 95  % CI, 1.01–2.74; p = 0.045). Greater obesity risk was also found in inactive or high carbohydrate intake subjects with the Ala12 allele of PPARG2 gene. Interestingly, subjects carrying the Ala allele of the PPARG2 gene and with a high CHO (>246 g/day) intake had an increased obesity risk compared to Pro12Pro subjects (OR, 2.67; 95 % CI, 1.3–5.46; p = 0.007; p for [CHO × PPARG2] interaction = 0.046). Moreover, in subjects with a high CHO intake, the co-presence of the Ala allele of PPARG2 gene and one minor A allele (rs9939609) of FTO gene did increase obesity risk (OR, 3.26; 95 % CI, 1.19–8.89; p = 0.021) when compared to non-carrier (Pro12Pro/TT) subjects. In conclusion, it appears that lifestyle factors may act as effect modifiers for obesity risk linked to Ala12 allele of the PPARG2 gene and the minor A allele of FTO gene in an elderly population.     

The primary structure of the β-subunit of protocatechuate 3,4-dioxygenase from Pseudomonas aeruginosa

The complete amino acid sequence of the β-subunit of protocatechuate 3,4-dioxygenase was determined. The β-subunit contained four methionine residues. Thus, five peptides were obtained after cleavage of the carboxymethylated β-subunit with cyanogen bromide, and were isolated on Sephadex G-75 column chromatography. The amino acid sequences of the cyanogen bromide peptides were established by characterization of the peptides obtained after digestion with trypsin, chymotrypsin, thermolysin, or Staphylococcus aureus protease. The major sequencing techniques used were automated and manual Edman degradations. The five cyanogen bromide peptides were aligned by means of the amino acid sequences of the peptides containing methionine purified from the tryptic hydrolysate of the carboxymethylated β-subunit. The amino acid sequence of all the 238 residues was as follows: ProAlaGlnAspAsnSerArgPheValIleArgAsp ArgAsnTrpHis ProLysAlaLeuThrPro-Asp — TyrLysThrSerIleAlaArg SerProArgGlnAla LeuValSerIleProGlnSer — IleSerGluThrThrGly ProAsnPheSerHisLeu GlyPheGlyAlaHisAsp-His — AspLeuLeuLeuAsnPheAsn AsnGlyGlyLeu ProIleGlyGluArgIle-Ile — ValAlaGlyArgValValAsp GlnTyrGlyLysPro ValProAsnThrLeuValGluMet — TrpGlnAlaAsnAla GlyGlyArgTyrArg HisLysAsnAspArgTyrLeuAlaPro — LeuAspProAsn PheGlyGlyValGly ArgCysLeuThrAspSerAspGlyTyrTyr — SerPheArg ThrIleLysProGlyPro TyrProTrpArgAsnGlyProAsnAsp — TrpArgProAla HisIleHisPheGlyIle SerGlyProSerIleAlaThr-Lys — LeuIleThrGlnLeuTyr PheGluGlyAspPro LeuIleProMetCysProIleVal — LysSerIleAlaAsn ProGluAlaValGlnGln LeuIleAlaLysLeuAspMetAsnAsn — AlaAsnProMet AsnCysLeuAlaTyr ArgPheAspIleValLeuArgGlyGlnArgLysThrHis PheGluAsnCys. The sequence published earlier in summary form (Iwaki et al., 1979, J. Biochem.86, 1159–1162) contained a few errors which are pointed out in this paper.     

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.     

Association of Histamine N-Methyltransferase Thr105Ile Polymorphism with Parkinson’s Disease and Schizophrenia in Han Chinese: A Case-Control Study

Parkinson’s disease (PD) and schizophrenia (SCZ) are frequent central nervous disorders that have unclear etiologies but that show similarities in their pathogenesis. Since elevated histamine levels in the brain have been associated with PD and SCZ, we wanted to explore whether the Thr105Ile substitution in the histamine N-methyltransferase gene (HNMT-Thr105Ile), which impairs histamine degradation, is associated with either disease. We used the ligase detection reaction to genotype a case-control cohort of Han Chinese patients with PD or SCZ and healthy controls at the HNMT-Thr105Ile locus. The Ile allele was associated with reduced risk of PD (OR 0.516, 95%CI 0.318 to 0.838, p = 0.007) and of SCZ (OR 0.499, 95%CI 0.288 to 0.865, p = 0.011). Genotype frequencies and minor allele frequencies were similar between patients and controls when we compared males with females or early-onset patients with late-onset ones. Genotype and allele frequencies were not significantly different between PD patients with dyskinesia and PD patients without dyskinesia. Our results suggest that the heterozygous Thr/Ile genotype at the HNMT-Thr105Ile locus and the minor Ile105 allele protect against PD and SCZ in Han Chinese.