Common polymorphisms in the P-selectin gene in women with recurrent spontaneous abortions

Background

To investigate possible associations of P-selectin polymorphisms with idiopathic recurrent pregnancy loss (RPL).

Methods

Study subjects comprised 270 consecutive RPL cases attending outpatient maternity services, and 322 multi-parous control women. P-selectin genotyping was done by PCR-RFLP and PCR-ASA methods.

Results

The P-selectin variants rs1800807, rs1800805, and rs6127, were in Hardy Weinberg equilibrium, and low linkage disequilibrium was noted between the three studied SNPs. The frequency of rs6127 A allele (P < 0.001I), but not rs1800807 C allele (P = 0.957) or rs1800805 A allele (P = 0.760), was higher in RPL cases than in control women. Significant differences in the distribution of rs6127 (P < 0.001), but not rs1800807 (P = 0.444) or rs1800805 (P = 0.391) genotypes were seen between cases and controls, and only rs6127 showed a significant association with RPL, with increments of 2.65 and 4.96 in disease risk seen for heterozygous and homozygous carriers, respectively. Among the 8 three-locus Pselectin haplotypes constructed (rs1800807/rs1800805/rs6127), increased frequency of GGG (Pc = 0.0249), CGG (Pc = 0.0256), and CAG (Pc = 0.0174) haplotypes, and lower frequency of CGA haplotype (Pc = 0.0091) were seen in RPL cases, thus conferring disease susceptibility and protective nature to these haplotypes, respectively.

Conclusions

P-selectin gene polymorphisms and haplotypes contribute to RPL development.     

Impact of Apo E gene polymorphism on HCV therapy related outcome in a cohort of HCV Egyptian patients

The functional apolipoprotein E (Apo E) gene polymorphism could be used as a determinant of outcome of HCV infection. This study aimed to demonstrate the impact of Apo E genotype on the response to HCV combined therapy. Material and methods: The study has been implemented on 125 individuals with persistent HCV infection and 120 cases with sustained virologic response (SVR). All participants were genotyped for ApoE gene polymorphism by a real-time quantitative PCR (qPCR). Results: Statistically significant differences were demonstrated regarding the Apo E genotypes between the two groups (P-value?<?.001) where the frequency of E3E3 was significantly higher among the chronic HCV-patients while E3E4 and E4E4 genotypes frequencies were higher among the SVR-subjects group and E3E3 genotype was associated with increased risk of chronicity (OR 4.7; 95% CI 1.9–12.1, P-value?<?.001). Moreover, There were statically significant differences regarding E3 and E4 alleles frequencies, where E3 allele display a higher frequency among the chronic HCV-patient group while the SVR-subjects group showed higher frequency of E4 allele and the carriers of E3 allele have 1.4 times more risk to develop chronicity than those with E4 allele (OR 1.4; 95% CI 1.0–2.0, P-value?<?.05). Meanwhile the protective E2 allele was absent in all infected participants. Conclusion: This study supports the hypothesis of the protective impact of Apo E4 allele that favors viral clearance of HCV infection and its recovery after combined therapy, while the Apo E3 allele is considered as a particular risk factor for the chronicity in HCV patients and resistance to therapy. Whereas the Apo E2 allele confers a resistance to HCV infection at a time of exposure.     

Association between apolipoprotein E gene polymorphism and the risk of multiple sclerosis: A meta-analysis of 6977 subjects

Epidemiological studies have evaluated the association between apolipoprotein E (ApoE) gene polymorphism and multiple sclerosis (MS) risk. However, the results remain conflicting. Therefore, in order to derive a more precise association of ApoE gene polymorphism with MS risk, we performed this meta-analysis. Systematic searches of electronic databases PubMed, Embase and Web of Science, as well as hand searching of the references of identified articles were performed. Twenty studies were identified, covering a total of 4080 MS cases and 2897 controls. The results showed evidence for significant association between ApoE ε2 mutation and MS risk (for ε2/ε4 versus ε3/ε3: OR = 1.74, 95% CI = 1.12–2.71, p = 0.01; for ε2 allele versus ε3 allele: OR = 1.16, 95% CI = 1.01–1.35, p = 0.04). In the subgroup analysis by ethnicity, the similar results were obtained among Europeans (for ε2/ε4 versus ε3/ε3: OR = 1.81, 95% CI = 1.14–2.87, p = 0.01; for ε2 allele versus ε3 allele: OR = 1.19, 95% CI = 1.02–1.38, p = 0.03). After excluding the outlier studies by observing Galbraith plot, marginal association was found between ApoE ε3/ε4 genotype and the protective factor for MS (for ε3/ε4 versus ε3/ε3: OR = 0.86, 95% CI = 0.75–0.99, p = 0.04). In summary, the present meta-analysis provides evidence that ApoE ε2 mutation is associated with MS risk. In addition, ApoE ε3/ε4 genotype appears to be a protective factor for MS.     

Apolipoprotein E gene polymorphisms in Lebanese with hypercholesterolemia

Apolipoprotein E (ApoE) has an important role in the metabolism of lipids through its major isoforms (ε2, ε3, ε4). In particular, ApoE ε4, has been considered as a major genetic risk factor for cardiovascular diseases (CVD). The aim of our study is to investigate the frequency of ApoE gene polymorphisms (rs 429358C > T, rs 7412C > T) and their relationship to lipid parameters in a group of Lebanese hypercholesterolemic subjects (22 males and 24 females, aged 25–80 years). Lipid profile, apolipoproteins A-I and B were determined using fasting serum samples; and molecular analysis of ApoE polymorphisms using blood in EDTA tubes. The distribution of the four ApoE genotypes detected in this study was: ε3/ε3 (73.9%), ε3/ε4 (17.4%), ε2/ε3 (6.5%), and ε2/ε4 (2.2%) resulting in allelic frequencies for ε2, ε3 and ε4 of 4.3%, 85.9% and 9.8%, respectively. No association was determined among any of the lipid parameters, gender and ApoE genotypes. Lipid parameters were not statistically different among various ApoE genotypes (p > 0.05). ApoE ε2 frequency was found to be lower than that previously reported for healthy Lebanese (7.2%). CVD is one of the major leading causes of mortality in Lebanon with a reported prevalence of 12.2% in males and 7.7% in females, which incidentally agrees with our finding regarding ε4 allelic frequency of 13.6% in males and 6.3% in females. Consequently, larger prospective studies are recommended to highlight the correlation of ApoE polymorphisms to other biochemical and environmental factors involved in CVD.     

The association of idiopathic recurrent pregnancy loss with polymorphisms in hemostasis-related genes

Recurrent pregnancy loss (RPL) is a complex, multifactorial condition. Inherited thrombophilia is the leading cause of thromboembolism and is associated with an increased risk of RPL. The aims of the current study were to investigate the effects of polymorphisms in hemostasis-related genes antithrombin (SERPINC1), thrombomodulin (THBD), tissue factor pathway inhibitor (TFPI), factor V, factor II and annexin A5 (ANXA5), involved in reproductive failure in 94 RPL cases with two or more consecutive pregnancy losses prior to 20 weeks of pregnancy and 169 healthy controls who had at least one term delivery and no history of pregnancy loss. The genotypes of SERPINC1 G786A, THBD C1418T, TFPI T-33C, factor V G1628A, factor II A19911G and ANXA5 G76A were assayed by the Sequenom MassARRAY system. Genotype and allele frequencies for SERPINC1 (rs2227589), TFPI (rs8176592), factor V (rs6020), factor II (rs3136516) and ANXA5 (rs113588187) in cases and controls were similar. The distribution of THBD C1418T allele showed significant differences between RPL cases and healthy controls (odds ratio (OR): 1.58, 95%, confidence interval (CI): 1.05–2.39, P = 0.027). In univariate logistic regression analyses, carriers of THBD 1418T allele (CT + TT) had an increased risk of RPL (OR: 1.83, 95%, CI: 1.10–3.06, P = 0.020). This indicated that THBD 1418T allele was associated with increasing the risk of RPL.     

Polymorphism of the apolipoprotein E gene and risk of multiple sclerosis in ethnic Russians

Multiple sclerosis (MS) is a multifactorial disease of the central nervous system with pronounced hereditary predisposition. The purpose of the study was to test the assumption on the involvement of the apolipoprotein E gene (APOE) polymorphism in exon 4 in the development of MS in ethnic Russians. Samples independently collected in Moscow (106 MS cases and 189 control healthy volunteers), Sverdlovsk oblast (54 and 109, respectively), and the Republic of Bashkortostan (119 and 285, respectively) were examined. Genotypes for 2059C/T and 2197C/T polymorphisms of the APOE gene, which determine the amino acid substitutions C112R and R158C in apolipoprotein E, were analyzed by polymerase chain reaction followed by restriction analysis of amplificates. No statistically significant differences in genotype or allele frequencies were found between the control group and the group of MS cases. The APOE*4 allele is not associated with the risk of MS in ethnic Russians.     

Is there any association of apolipoprotein E gene polymorphism with obesity status and lipid profiles? Tehran Lipid and Glucose Study (TLGS)

Aims

Considering the key role played by the apolipoprotein E (Apo E) gene in the regulation of lipid metabolism and obesity, the current study has evaluate the association between abdominal obesity and Apo E gene polymorphism in a population of Tehran.

Materials and methods

A cross-sectional study was performed on 345 men and 498 women, aged 19–86 years, selected from among participants of the Tehran Lipid and Glucose Study. The RFLP-PCR technique was employed to investigate polymorphism in the gene fragments. Based on the national survey of risk factors for non-communicable diseases of Iran, waist circumference (WC) cut off was set at 89 cm for men and 91 cm for women. The risk effect of obesity related variables and lipid profiles in two groups of WC were examined by logistic regression. For body mass index (BMI), waist to hip ratio (WHR), high-density lipoprotein-cholesterol (HDL-C), triglyceride (TG), fasting blood sugar (FBS), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and blood pressure (BP), the standard risk cut-offs were applied.

Results

Frequencies of E2, E3, and E4 alleles were 9.7, 73, and 14.6%, respectively. The presence of the E3 allele was significantly associated with higher TG level in subjects with high WC, while, the presence of E4 allele decreased the plasma HDL-C (E2:52.1 ± 13.1 vs., E3:48.9 ± 11.2 vs., E4:44.6 ± 10.6 mg/dl, p < 0.05), HDL-C2 (E2:20.4 ± 9.2 vs., E3:19.1 ± 8.8 vs., E4:16.3 ± 7.9 mg/dl, p < 0.05), and HDL-C3 (E2:32.1 ± 7.4 vs., E3:30.3 ± 6.2 vs., E4:28.3 ± 6.1 mg/dl, p < 0.05) in normal WC subjects. The presence of the E3 carrier increased the risk of having higher plasma TG, compared with the E2 carrier (95% CI OR = 1.91, 1.02–3.57; p = 0.04).

Conclusion

According to the results of this study, the E3 carrier, caused an approximately 90% increase in the levels of TG in the group with abdominal obesity.     

Logic regression analysis of association of gene polymorphisms with low HDL: Tehran Lipid and Glucose Study

Introduction

Logic regression is a generalized regression method that can recognize complex Boolean interactions of binary variables. It has been successfully applied to single-nucleotide polymorphism (SNP) data because of the importance of interactions in SNP association studies. The objective of this study is to assess the association between high-density lipoprotein (HDL) function and some related gene polymorphisms after adjusting for potential confounders using logic regression.

Methods

Subjects in this cross-sectional study were randomly selected from among participants of the Tehran Lipid and Glucose Study (TLGS). A total of 436 subjects (172 men and 264 women), aged ≥ 20 years, were selected to be included in the current study. Logic regression analysis was used in order to recognize the combination of genetic main effects and possible interactions associated with HDL-C level. Cross validation and randomization test were carried out to avoid over fitting of the models.

Results

The cross validation test suggested three Boolean combinations with four predictors for a fully-adjusted logic model. The fully adjusted model showed that those who carry an Apo E gene E3 allele or have high TG level have an odds ratio of 2.35 (95% CI:1.3–4.25) for having low HDL compared to other subjects. In addition, subjects with high TG level have an odds ratio of 2.73 (95% CI: 1.65, 4.53) for having low HDL.

Conclusion

The results showed that logic regression is a powerful method to find the interaction between high TG level and Apo E polymorphism associated with low HDL.     

Dietary fat and apolipoprotein genotypes modulate plasma lipoprotein levels in Brazilian elderly women

Studies show that genetic polymorphisms in apolipoproteins, which are in charge of lipid transport, predispose to atherogenic dyslipidemia. This study aimed to investigate the impact of apolipoprotein E, A5, and B genotypes and dietary intake on lipid profile in a sample of elderly women in Brazil. Two hundred and fifty-two women (60 years or older) living in the outskirts of the Brazilian Federal District underwent clinical and laboratory assessments to characterize glycemic and lipidemic variables, and also to exclude confounding factors (smoking, drinking, hormone replacement, cognitive impairment, physical activity). Three-day food records were used to determine usual dietary intake, whereas genotypic evaluations were in accordance to established methodologies. Genotype frequencies were consistent with the Hardy–Weinberg equilibrium. Prior to adjustment, individuals carrying the ε2 allele showed higher serum levels of triglycerides (P < 0.05) and VLDL (P < 0.005) compared to ε4 carriers, whereas LDL levels were considerably elevated in ε4 compared to ε2 carriers. In the presence of high intake of total fat or a low ratio of polyunsaturated to saturated fatty acid, ε4 carriers lost protection against hypertriglyceridemia. There was no association of the apolipoprotein A5 and B genotypes with lipidemic levels independently of the fat intake regimen. Results are suggestive of a dysbetalipoproteinemic-like phenotype in postmenopausal women, with remarkable gene–diet interaction.     

载脂蛋白E基因多态性与动脉粥样硬化性脑梗塞关系的研究

应用聚合酶链反应(PCR)扩增ApoE基因外显子4中编码112位和158位氨基酸的 DNA片段,将该长为292bp的PCR产物以HhaI酶切,根据其限制性片段长度多态性图谱确定ApoE基因型。对广东汉族人群的50例动脉粥样硬化脑梗塞(ACI)患者和50例健康对照者的ApoE基因多态性频率的研究结果表明:所研究的人群中,ApoE基因多态性频率与ACI没有关联。ACI患者中各基因型亚组之间血清TG和TC浓度无显著性差异。 Abstract:The polymerase chain reaction(PCR)and restriction fragment length polymorphism techniques(RFLPs)were used to study the relation between apolipoprotein E gene polymorphism and atherosclerotic cerebral infarction(ACI).A 292 bp DNA fragment containing codes for the 112 and 158 amino acid residues in the fourth exon of ApoE gene was amplified by PCR.The PCR products were digested with HhaI.The polymorphism patterns of Apo E gene,allele frequencies in 50 Chinese healthy and 50 patients with ACI,and the serum levels of TG and TC in the different subgenotypes of 50 patients with ACI were detected.,no statistical significant differences of alleles frequencies were found between the cases with ACI and the control,and no statistical significant differences of the serum levels of TG and TC were found among the different subgenotypes of 50 patients with ACI.These results suggested that ApoE gene polymorphism was not associated with the development of ACI.     

Genetic variants of estrogen beta and leptin receptors may cause gynecomastia in adolescent

Objective

Gynecomastia is a benign breast enlargement in males that affects approximately one-third of adolescents. The exact mechanism is not fully understood; however, it has been proposed that estrogen receptors and aromatase enzyme activity may play important roles in the pathogenesis of gynecomastia. While many studies have reported that aromatase enzyme (CYP19) gene polymorphism is associated with gynecomastia, only one study has shown a relationship between estrogen receptor (ER) alpha and beta gene polymorphism and gynecomastia. Thus, the aim of this study was to evaluate the relationships between CYP19 (rs2414096), ER alpha (rs2234693), ER beta (rs4986938), leptin (rs7799039), and leptin receptor (rs1137101) gene polymorphisms and gynecomastia.

Methods

This study included 107 male adolescents with gynecomastia and 97 controls. Total serum testosterone (T) and estradiol (E2) levels were measured, and DNA was extracted from whole blood using the PCR–RFLP technique. The polymorphic distributions of CYP19, ER alpha, ER beta, leptin and leptin receptor genes were compared.

Results

The median E2 level was 12.41 (5.00–65.40) pg/ml in the control group and 16.86 (2.58–78.47) pg/ml in the study group (p < 0.001). The median T level was 2.19 (0.04–7.04) ng/ml in the control group and 1.46 (0.13–12.02) ng/ml in the study group (p = 0.714). There was a significant relationship between gynecomastia and leptin receptor rs1137101 (p = 0.002) and ER beta receptor rs4986938 gene polymorphisms (p = 0.002).

Conclusions

According to our results, increased E2 level and ER beta gene rs4986938 polymorphism might explain why some adolescents have gynecomastia. Leptin receptor gene rs1137101 polymorphism might affect susceptibility to gynecomastia.     

How proteomic ApoE serotyping could impact Alzheimer’s disease risk assessment: genetic testing by proteomics

Humans have three major apolipoprotein E (ApoE) alleles (APOE; ε2, ε3 and ε4) that produce three ApoE protein isoforms. The ε2 allele encodes the ApoE2 isoform (Cys112, Cys158), whereas ε3 encodes the wild-type ApoE3 isoform (Cys112, Arg158) and ε4 encodes the ApoE4 isoform (Arg112, Arg158). Because the type of ApoE expressed is related to sporadic Alzheimer’s disease risk and familial hyperlipidemia, many clinical studies have utilized ApoE typing in recent years. ApoE serotyping is based on the correlation between ApoE genotype and isoform; it is therefore possible to determine the genotype from the blood ApoE isoform combination. Serotyping ApoE using mass spectrometry promises highly accurate results while requiring minimal amounts of blood and reagents, resulting in lower costs, which suggest that proteomic-based ApoE serotyping may eventually become a routine clinical laboratory test. Not limited to ApoE, proteomic analysis of human samples could be used to intentionally determine – and perhaps unintentionally reveal – personal genetic information.     

Apo E gene polymorphism on development of diabetic nephropathy

Type 2 diabetes causes premature morbidity and mortality due to the complications of atherosclerosis and diabetic nephropathy (DN). Polymorphism of Apo E gene is known to influence lipid metabolism. Apo E is polymorphic, consisting of three common isoforms (epsilon2, epsilon3 and epsilon4) encoded by three alleles (2, 3 and 4) in exon 4 on chromosome 19. The aim of this study was to investigate the effect of Apo E polymorphism as a prognostic risk factor for the development of DN. A total of 108 NIDDM patients were recruited from the Nephrology and Endocrinology Departments of our hospital. All subjects were divided into three groups: Group I: diabetes with nephropathy (n:37), group II: diabetes without nephropathy (n:71), group III: controls (n:46). Apo E genotypes were determined by real-time PCR. The epsilon4 allele frequency was significantly higher in-group I (10.8%) than in-group III (2.2%), (p < 0.05). In diabetics without nephropathy, the total cholesterol and LDL cholesterol levels were significantly lower in subjects with epsilon2 alleles than epsilon3 and epsilon4 alleles. In conclusion, the present prospective study indicates that the epsilon4 allele of the Apo E polymorphism is one of the prognostic risk factors involved in the development of DN with type 2 diabetes mellitus.     

Association of APOE, GCPII and MMP9 polymorphisms with common diseases and lipid levels in an older adult/elderly cohort

Background and aims

The characterization of candidate gene polymorphisms in elderly populations is an important tool for the identification of risk factors for age-related diseases and conditions. We aimed to genotype the APOE polymorphisms (rs429358 and rs7412), rs61886492 (1561C>T) and rs202720 of GCPII gene and rs3918242 (− 1562C>T) of MMP9 gene in an older-adult/elderly cohort from Cuiabá city, Mato Grosso Brazil as well as to characterize risk factors for morbidities and conditions affecting this cohort.

Methods

The studied population consisted of 570 subjects from Cuiabá city, Brazil, who were subjected to clinical interviews and blood collection for laboratory examinations and DNA extraction. Restriction Fragment Length Polymorphism Polymerase Chain Reaction (RFLP-PCR), sequence-specific primer PCR (SSP-PCR) and TaqMan® allelic discrimination assay were used for genotyping.

Results

The frequencies of APOE ε2 and ε4 were 6.6% and 14.8%, respectively, and the frequencies of GCPII rs61886492 T allele, GCPII rs202720 C allele and MMP9 rs3918242 T allele were, respectively, 3.0%, 26.6% and 10.1%. Significant associations between APOE ε2 allele with lower total cholesterol and LDL-cholesterol were found. In addition, MMP9 rs3918242 T allele was associated with higher LDL-cholesterol levels, suggesting a link between lipid metabolism alteration and cardiovascular disease.

Conclusions

The present findings contributed to characterize risk factors specific for the studied population and to better understand the molecular physiopathology of common morbidities and conditions affecting older-adult/elderly people.     

Lipid class composition of membrane and raft fractions from brains of individuals with Alzheimer's disease

Perturbation of the homeostasis of brain membrane lipids has been implicated in the pathomechanism of Alzheimer's disease (AD). The ε4 allele of the apolipoprotein E gene (APOE) confers an increased risk, in a dosage-dependent manner, for brain amyloid-β accumulation and the development of sporadic AD. An effect of the APOE genotype on brain lipid homeostasis may underlie the AD risk associated with the ε4 allele. In this research, we examined an effect of APOE ε4 on the lipid class composition of crude membranes and raft-enriched fractions of brains. We applied enzymatic reaction-based methods for the quantification of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidic acid, and sphingomyelin. Our results indicate that brain lipid class composition was neither significantly altered in AD subjects nor affected by the presence of the APOE ε4 allele.     

p53 signaling pathway polymorphisms associated to recurrent pregnancy loss

The p53 protein is known for performing essential functions in the maintenance of genomic stability in somatic cells and prevention of tumor formation. Studies of the p53 signaling pathway have suggested associations between some polymorphisms and infertility, post-in vitro fertilization implantation failure and recurrent abortions. The TP53 Pro72Arg polymorphism has been implicated as a risk factor for recurrent pregnancy loss (RPL); however, the association is controversial. In this study, our objective was to evaluate selected polymorphisms in genes of the p53 signalling pathway [TP53 c.215G>C (Pro72Arg), MDM2 c.14+309T>G (SNP309) and LIF c.1414T>G in the region 3′ UTR] and determine their effect as risk factors for RPL. In a case–control study, we investigated 120 women with two or more pregnancy losses and 143 fertile control women reporting at least two live births and no history of pregnancy loss. When analyzed separately, the allele and genotype distributions of the polymorphisms in the two groups were not different. However, in a multivariate analysis adjusted for alcohol consumption, smoking, ethnicity, and number of pregnancies, the interaction between the genotypes TP53 Arg/Arg (rs1042522) and MDM2 TT (rs2279744) showed to be associated to RPL, increasing the risk for this condition (OR = 2.58, 95 % CI: 1.31–5.07, p = 0.006). In conclusion, our study indicates that the combination of TP53 Arg/Arg (rs1042522) and MDM2 TT (rs2279744) genotypes may be a risk factor for RPL.     

Multi-drug resistance-1 gene polymorphisms in nephrotic syndrome: Impact on susceptibility and response to steroids

Background

Role of multidrug resistance-1 (MDR-1) gene polymorphisms has not been clarified in nephrotic syndrome (NS). Additionally, researchers studied several genetic polymorphisms to explain their influence on different patients' responses to steroid; however the data were inconsistent. Therefore, we aimed to investigate the association of MDR-1 gene polymorphisms [C1236T, G2677T/A, C3435T] and haplotypes with susceptibility to childhood nephrotic syndrome, and whether they influence steroid response.

Methods

We detected MDR-1 gene polymorphisms using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) in 138 NS patients and 140 age and sex matched healthy children.

Results

The frequencies of MDR1 G2677T/A GT, GA, TT + AA genotypes or T allele, MDR1 C3435T TT genotype, and T allele genotype frequencies were significantly increased in NS group. While no significant differences were observed in distributions of C1236T genotypes or allele between NS patients and healthy children. Moreover, steroid non-responder NS patients had significantly higher frequencies of MDR1 G2677T/A GT, GA, and TT + AA genotypes than steroid responsive NS patients. We observed also that NS patients with age less than 6 years old had increased frequencies of MDR1 G2677T/A GT, GA, TT + AA genotypes or T allele MDR1 C3435T CT, TT genotypes and T allele. Interestingly the frequency of the TGC haplotype of MDR1 was lower in the initial steroid responders than in non-responders NS patients. On the contrary, there were no any association between the MDR1 haplotypes with NS susceptibility and they did not influence renal pathological findings.

Conclusion

Our data suggested that MDR1 C3435T or G2677T/A gene polymorphisms are risk factors of increased susceptibility, earlier onset of NS, and steroid resistance.     

Polymorphism of Apolipoproteine E in Relation with Alzheimer and Vascular Dementia

Summary 1. The epsilon 4 allele of the apolipoprotein E gene increases the risk of late onset familial and sporadic Alzheimer disease. Relation of epsilon 4 allele of the apolipoprotein E gene to various types of dementia and the onset of dementia were analyzed in the present study.2. The study comprised 139 patients (50 men and 89 women) with dementia, mean age 73.61 years (range 47–98). The diagnosis of dementia was made according to Diagnostic and Statistical Manual of Mental Disorders, and subtypes diagnoses were made according to NINCDS-ADRDA and NINDS-AIREN criteria. Minimental State Examination (MMSE) was used for the screening of dementia. Apolipoprotein E polymorphism was determined by the PCR-RFLP technique-polymerase chain reaction and subsequent digestion with specific restriction endonuclease. For statistical analyses chi-square test and the crude Gart′s odds ratio (OR) and 95% confidence intervals (CI) were used.3. From 139 dementia patients (MMSE ≤24 points) in 61 (45%) Alzheimer disease (AD) was present, in 44 patients (31%) vascular dementia (VD), and in 34 (24%) mixed dementia (MD) were revealed. In comparison with control group the presence of at least one ApoE-ɛ4 allele was significantly higher only in the group with AD (p < 0.001), (OR=2.76; 95%: 1.42–5.36). The frequency of ɛ4 allele carriers was significantly overrepresented in AD group compared with VD (χ²=5.94; p=0.0148). Differences between AD and MD or VD and MD were not confirmed.     

Polymorphisms of human histamine receptor H4 gene are associated with breast cancer in Chinese Han population

Previous investigations indicated that histamine receptor H4 (HRH4) played important roles in many aspects of breast cancer pathogenesis, and that the polymorphisms of HRH4 gene may result in expression and functional changes of HRH4 proteins. However, the relationship between polymorphisms of HRH4 and breast cancer risk and malignant degree is unclear. In the present study, we conducted a case–control investigation among 185 Chinese Han breast cancer patients and 199 ethnicity-matched health controls. Four tag-SNPs (i.e. rs623590, rs16940762, rs11662595 and rs1421125) of HRH4 were genotyped and association analysis was performed. Odds ratios (ORs) with 95% confidence intervals (CI) were used to assess the association. We found that the T allele of rs623590 had a decreased risk of breast cancer (adjusted OR, 0.667; 95% CI, 0.486–0.913; P = 0.012) while the A allele of rs1421125 had an increased risk (adjusted OR, 1.653; 95% CI, 1.139–2.397; P = 0.008). Further haplotype analysis showed that the CAA haplotype of rs623590–rs11662595–rs1421125 was more frequent among patients with breast cancer (adjusted OR, 1.856; 95% CI, 1.236–2.787; P = 0.003). Additionally, polymorphisms of rs623590 and rs11662595 were also correlated with clinical stages, lymph node involvement, and HER2 status. These findings indicated that the variants of rs623590, rs11662595 and rs1421125 genotypes of HRH4 gene were significantly associated with the risk and malignant degree of breast cancer in Chinese Han populations, which may provide us novel insight into the pathogenesis of breast cancer although further studies with larger participants worldwide are still needed for conclusion validation.     

Apolipoprotein E genotyping in Turkish myocardial infarction survivors and healthy controls

The apolipoprotein (Apo) E gene is known to be polymorphic. Three common alleles determine six phenotypes which can easily be detected by restriction fragment length polymorphism. We performed apo E genotyping in myocardial infarction survivors and healthy controls for the first time in the Turkish population. DNA was amplified by polymerase chain reaction (PCR) and the PCR product was digested with restriction enzymesHhaI to detect apo E2, E3, E4 and withTaqI to detect apo E1. Relative allele frequency for the patient group was found to be 0.91 for E3, 0.07 for E2, 0.02 for E4 and for the control group 0.875 for E3, 0.067 for E2, 0.058 for E4.