Genetic association of the P-glycoprotein gene ABCB1 polymorphisms with the risk for steroid-induced osteonecrosis of the femoral head in Chinese population

Steroid administration, which is commonly performed for the treatment of autoimmune inflammatory diseases, cancers or organ transplantation, has been a leading cause of nontraumatic osteonecrosis of the femoral head (ONFH). Single nucleotide polymorphisms (SNPs) of the adenosine triphosphate-binding cassette B1 (ABCB1) gene have been demonstrated to be related to steroid-induced ONFH in small sample sizes of Japanese kidney failure and Chinese systemic lupus erythematosus patients. However, there are obvious controversial results in the relationship of ABCB1 gene polymorphisms with steroid-induced ONFH. The aim of this study was to validate the genetic association of ABCB1 polymorphisms with the risk for steroid-induced ONFH in a large cohort of Chinese population. A case–control study was conducted, which included 94 and 106 unrelated patients after steroid administration recruited from 14 provinces in China, respectively. Two SNPs (rs1045642 and rs2032582) within ABCB1 were genotyped using Sequenom MassARRAY system. Multivariate analyses based on clinical information were performed to determine the associations between the SNPs and risk of steroid-induced ONFH. rs1045642 SNP was significantly associated with steroid-induced ONFH group in codominant (P = 0.02), recessive (P = 0.006) and overdominant (P = 0.03) models. However, there were no differences found in genotype frequencies of rs2032582 SNP between controls and patients with steroid-induced ONFH (all P > 0.05). These findings suggested that rs1045642 SNP of ABCB1 may be associated with the risk of steroid-induced ONFH. Thus, it is useful to analyze this polymorphism for identifying high-risk individuals before the administration of steroids.     

The association of apolipoprotein E gene polymorphisms with cerebral palsy in Chinese infants

Apolipoprotein E (APOE, protein; ApoE, gene) is a lipid transport protein abundantly present in brain cells. Previous studies have suggested that there is an association between genetic variants of ApoE and susceptibility to cerebral palsy (CP). The purpose of this study was to explore whether the ApoE gene is involved in the etiology of CP in the Chinese population. In this study, 350 CP patients and 242 healthy control children were recruited. Genomic DNA was prepared from venous blood and all five single nucleotide polymorphisms (SNPs) in ApoE (rs769446, rs405509, rs121918399, rs429358, and rs190853081) were detected by the MassARRAY platform-based genotyping approach. The SHEsis program was used to analyze the genotyping data, and we systemically analyzed the association of the ApoE SNPs with different subtypes of CP. No significant association was detected between the e4 identified by the C allele of rs429358 and CP, but there were significant differences in allelic frequencies between the CP patients and controls at rs769446 (P = 0.005, P = 0.025 after Bonferroni correction), as well as between the CP patients with preterm birth (<34 gestational weeks) and controls at rs769446 (P = 0.001, P = 0.005 after Bonferroni correction). A haplotype consisting of the five SNPs rs769446(C), rs405509(C), rs121918399(C), rs429358(T), and rs190853081(G) was associated with a decreased risk of CP (P = 0.002 after Bonferroni correction). However, we found no significant association between any of the other three SNPs and CP based on different subgroup analyses. This study provides the first evidence that ApoE gene polymorphisms are a potential risk factor for CP in the Chinese population.     

The Apolipoprotein E Polymorphism rs7412 Associates with Body Fatness Independently of Plasma Lipids in Middle Aged Men

Background

The apolipoprotein E (APOE) gene is polymorphic, encoding one of 3 common alleles (ε2, ε3, ε4) produced from combinations of 2 non-synonymous SNPs (rs429358 and rs7412). APOE plays an important role controlling plasma lipids but its association with adipocyte functionality and body fatness remains to be determined.

Methods

We analyzed fasting plasma lipids and genotyped the two main APOE-SNPs (rs429358 and rs7412), both located in the fourth exon of the APOE, in 4660 Caucasian middle-aged men free of cardiovascular disease.

Results

The rs7412 SNP, which determines the APOE2 isoform, was significantly associated with Body Mass Index (BMI) and Waist Girth (WG) in a multivariate model accounting for age, smoking status and plasma lipids. BMI and WG were highest in TT homozygotes and lowest in CC homozygotes. This effect was independent of the rs429358 SNP, which failed to show any association with the BMI and WG variables. The odds ratio of being obese (BMI>30) for individuals carrying the APOε2 allele, present in 14% of the cohort and defined by the rs7412 SNP, was also significant in this multivariate model, with an OR of 1.27 (95% CI: 1.01–1.59).

Conclusions

This study provides an evidence of a lipid-independent association between the APOE SNP rs7412 and body fatness surrogates, BMI and WG, in a large cohort of middle-aged males.     

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.     

Genetic variants in MARCO are associated with the susceptibility to pulmonary tuberculosis in Chinese Han population

Background

Susceptibility to tuberculosis is not only determined by Mycobacterium tuberculosis infection, but also by the genetic component of the host. Macrophage receptor with a collagenous structure (MARCO) is essential components required for toll like receptor-signaling in macrophage response to Mycobacterium tuberculosis, which may contribute to tuberculosis risk.

Principal Findings

To specifically investigated whether single nucleotide polymorphisms (SNPs) in MARCO gene are associated with pulmonary tuberculosis in Chinese Han population. By selecting tagging SNPs in MARCO gene, 17 tag SNPs were identified and genotyped in 923 pulmonary tuberculosis patients and 1033 healthy control subjects using a hospital based case-control association study. Single-point and haplotype analysis revealed an association in intron and exon region of MARCO gene. One SNP (rs17009726) was associated with susceptibility to pulmonary tuberculosis, where the carriers of the G allele had a 1.65 fold (95% CI = 1.32–2.05, p _corrected = 9.27E–5) increased risk of pulmonary tuberculosis. Haplotype analysis revealed that haplotype GC containing G allele of 17009726 and haplotype TGCC (rs17795618T/A, rs1371562G/T, rs6761637T/C, rs2011839C/T) were also associated with susceptibility to pulmonary tuberculosis (p _corrected = 0.0001 and 0.029, respectively).

Conclusions

Our study suggested that genetic variants in MARCO gene were associated with pulmonary tuberculosis susceptibility in Chinese Han population, and the findings emphasize the importance of MARCO mediated immune responses in the pathogenesis of tuberculosis.     

Association of CELSR2, APOB100, ABCG5/8, LDLR,and APOE polymorphisms and their genetic risks with lipids among the Thai subjects

BackgroundHypercholesterolemia is a common cardiovascular risk factor. The aim of this study was to investigate the association of CELSR2 (rs629301), APOB100 (rs1367117), ABCG5/8 (rs6544713), LDLR (rs6511720), and APOE (rs429358, rs7412) polymorphisms, and their genetic risk scores with lipids among Thai subjects.MethodsA total of 459 study subjects (184 males, and 275 females) were enrolled. Blood pressure, serum lipids, and fasting blood sugar were measured. CELSR2 (rs629301), APOB100 (rs1367117), ABCG5/8 (rs6544713), and LDLR (rs6511720) polymorphisms were analyzed using PCR-HRM. APOE (rs429358, rs7412) polymorphism was analyzed using PCR-RFLP.ResultsTotal cholesterol (TC) levels were significantly higher in APOB100 AA genotype compared with GG, or AA + AG genotypes in total subjects. In addition, significantly higher concentrations of TC and low density lipoprotein cholesterol (LDL-C) were observed in APOE4 carriers compared to APOE2 carriers in total subjects, males, and females. The significantly higher concentrations of TC were observed in APOE4 carriers compared to APOE3 carriers in females. Moreover, the concentrations of TC, and LDL-C were significantly increased with genetic risk scores of APOB100, and APOE polymorphisms in total subjects, and females. There was no association between CELSR2 (rs629301), ABCG5/8 (rs6544713), and LDLR (rs6511720) polymorphisms and serum lipids.ConclusionAPOB100 (rs1367117), and APOE (rs429358, rs7412) but not CELSR2 (rs629301), ABCG5/8 (rs6544713), and LDLR (rs6511720) polymorphisms were associated with serum lipids. The cumulative risk alleles of APOB100 (rs1367117), and APOE (rs429358, rs7412) polymorphisms could enhance the elevated concentrations of TC, and LDL-C, and they may be used to predict severity of hypercholesterolemia among Thai subjects.     

Association between single-nucleotide polymorphisms in pre-miRNAs and the risk of asthma in a Chinese population

Single-nucleotide polymorphisms (SNPs) in pre-miRNAs may alter microRNA (miRNA) expression levels or processing and contribute to susceptibility to a wide range of diseases. We investigated the correlation between four SNPs (rs11614913, rs3746444, rs2910164, and rs229283) in pre-miRNAs and the risk of asthma in 220 asthma patients and 540 controls using polymerase chain reaction-restriction fragment length polymorphism methodology and DNA-sequencing. There were significant differences in the genotype and allelic distribution of rs2910164G/C and rs2292832C/T polymorphisms among cases and controls. The CC genotype and C allele of rs2910164G/C were significantly associated with a decreased risk of asthma (CC vs. GG, odds ratio [OR]?= 0.51, 95% confidence interval [CI]: 0.31-0.82; C vs. G, OR = 0.74, 95% CI: 0.59-0.93). Similarly, the TT genotype and T allele of rs2292832C/T were significantly associated with a decreased risk of asthma (TT vs. CC, OR = 0.56, 95% CI: 0.33-0.95; T vs. C, OR = 0.71, 95% CI: 0.53-0.95). However, no significant association between the other two polymorphisms (i.e., rs11614913C/T and rs3746444C/T) and the risk of asthma was observed. Our data indicate that rs2910164G/C and rs2292832C/T may play a role in the development of asthma.     

Association of IL‐37 gene polymorphisms with susceptibility to tuberculosis in Saudi subjects

Tuberculosis (TB) is one of the most common infectious diseases worldwide. IL‐37, a novel member of the IL‐1 family, has anti‐inflammatory activity. Various cytokine genes polymorphisms are reportedly associated with susceptibility to TB infection. However, an association between genetic variations in the IL‐37 gene and susceptibility to TB infection has not been investigated. The aim of this case‐control study was therefore to identify such an association in Saudi subjects, in which five single‐nucleotide polymorphisms (SNPs) in the IL‐37 gene were assessed. Serum concentrations of IL‐37 were evaluated using ELISA, and genetic variants genotyped by multiplex PCR and ligase detection reaction. It was found that the C/C genotype of rs2723176 (–6962 A/C) occurs significantly more frequently in patients with active TB and that the C allele of this SNP is associated with TB. In addition, the C allele of rs2723176 SNP was associated with high circulating concentrations of IL‐37. However, the genotype and allele frequency of the other four SNPs (rs3811046, rs3811047, rs2723186 and rs2723187) were not significantly associated with TB infection. In conclusion, the present data suggest that rs2723176 SNP of IL‐37 is involved in the development of TB infection. Furthermore, high circulating concentrations of IL‐37 may have a negative effect on protective immunity against TB infection.     

Pleiotropy and allelic heterogeneity in the TOMM40-APOE genomic region related to clinical and metabolic features of hepatitis C infection

Hepatitis C virus (HCV) modulates host lipid metabolism as part of its lifecycle and is dependent upon VLDL for co-assembly and secretion. HCV dyslipidemia is associated with steatosis, insulin resistance, IL28B genotype and disease progression. Apolipoprotein E (ApoE) is an important lipid transport protein, a key constituent of VLDL, and is involved in immunomodulation. Our aims were to determine the role of APOE regional polymorphisms on host lipids, IL28B genotype and disease severity in chronic HCV (CHC) patients. The study cohort included 732 CHC patients with available DNA for genotype determination of four polymorphisms in the chromosome 19 region that encompasses the TOMM40, APOE and APOC1 genes. Serum lipid analysis and apolipoproteins levels were measured using an immunoturbidimetric assay. APOE rs7412 polymorphism (capturing the ε2 isoform) was significantly associated with serum ApoE levels in both Caucasians and African-American patients (p?=?2.3?×?10^?11) and explained 7?% of variance in serum ApoE. Among IL28B-CC patients (n?=?196), the rs429358 (defines ε4 isoform) and TOMM40 ‘523’ S polymorphisms were associated with 12?% of variance in ApoB levels. Patients homozygous for the APOE ε3 isoform had a greater than twofold increased odds of F2–F4 fibrosis (p?=?1.8?×?10^?5), independent of serum lipid and lipoprotein levels. There were no associations between APOE polymorphisms and serum HDL-C, APO-CIII and triglycerides. In CHC patients, genetic heterogeneity in the APOE/TOMM40 genomic region is significantly associated with variation in serum ApoE and ApoB levels, and also with fibrosis suggesting a pleiotropic attribute of this genomic region.     

Lack of association of MTHFR gene polymorphisms with the risk of osteonecrosis of the femoral head in a Korean population

Some studies have suggested that coagulation disorders may be implicated in osteonecrosis of the femoral head (ONFH). The C677T polymorphism of the 5, 10-methylenetetrahydrofolate reductase (MTHFR) gene has been postulated to be a genetic risk factor for venous thromboembolism and osteonecrosis in Caucasians, but this relationship has not been established in other populations. In this study, we conducted case-control analysis of whether MTHFR polymorphisms are associated with ONFH in Korean patients. Fifteen single nucleotide polymorphisms (SNPs) were selected and genotyped in 443 ONFH patients and 273 control subjects using the TaqMan 5′ allelic discrimination assay. Comparison of ONFH and control subjects using logistic regression models revealed no statistically significant differences in the frequencies of the MTHFR polymorphisms and haplotypes. Further analysis stratified by etiology also showed no association. These results suggest that MTHFR polymorphisms play no significant role in susceptibility to ONFH in the Korean population.     

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 analysis of tissue factor pathway inhibitor polymorphisms and haplotypes with osteonecrosis of the femoral head in the Korean population

Thrombophilia and hypofibrinolysis have been implicated in the pathogenesis of osteonecrosis of the femoral head (ONFH). Tissue factor pathway inhibitor (TFPI), a multivalent protease inhibitor, is an important regulator of the tissue factor-mediated blood coagulation pathway. Mutations of the TFPI gene can increase the risk of thrombin generation and venous thrombosis. The aim of this study was to evaluate the association of TFPI gene polymorphisms with ONFH. All exons and their boundaries of the TFPI gene, including the -1500 bp promoter region, were directly sequenced in 24 Korean individuals and four sequence variants were identified. These four polymorphisms [-51096 G > A (C-399T), -50984A > G (T-287C), + 24999A > G (Int7 -33T > C), + 37339T > A] were genotyped in 474 ONFH patients and 349 control subjects. The association of genotyped SNPs with ONFH was not found in the present study. The haplotype AAAT of TFPI was significantly associated with total, alcohol-induced, and idiopathic ONFH (p = 0.003, 0.021, and 0.007, respectively), and the haplotype GAAT was significantly associated with total and alcohol ONFH (p = 0.022 and 0.009, respectively). In addition, a new SNP + 37339 T > A in the 3'-UTR of the TFPI gene, was found in the Korean population. To date, this study is the first to show that haplotypes of the TFPI gene are associated with an increased susceptibility for ONFH. The results suggest that genetic variations in TFPI may play an important role in the pathogenesis and risk factors of ONFH.     

The APOE4 allele is associated with a decreased risk of retinopathy in type 2 diabetics

Background

Common polymorphisms within the apolipoprotein E (APOE) gene are suggested to be associated with the development of type 2 diabetes mellitus (T2DM), but the potential association with T2DM complications (nephropathy, neuropathy and retinopathy) remains unclear. We perform the case–control study to analyse the association between the APOE polymorphism and risk of T2DM and to analysed the potential relationship between the APOE and T2DM complications.

Methods and results

APOE variants (rs429358 and rs7412) were genotyped by TaqMan assay in T2DM patients (N?=?1274; N?=?829 with complications including retinopathy, neuropathy and nephropathy status) and with PCR–RFLP in healthy nondiabetic controls (N?=?2055). The comparison of subjects with genotypes associated with low plasma cholesterol (APOE2/E2 and APOE2/E3 carriers vs. others) did not show an association with T2DM (OR [95% CI]?=?0.88 [0.71–1.08). The differences remained insignificant after adjusting for diabetes duration, sex and BMI. Carriers of at least one APOE4 allele (rs429358) are protected against T2DM related retinopathy (OR [95% CI]?=?0.65 [0.42–0.99]. Protection against retinopathy is driven mostly by females (OR [95% CI]?=?0.50 [0.25–0.99]); and remains significant (P?=?0.044) after adjustment for diabetes duration and BMI.

Conclusion

Common APOE polymorphism was not associated with T2DM in the Czech population. Yet, APOE4 allele revealed an association with retinopathy. In particular, female T2DM patients with at least one APOE4 allele exhibit lower prevalence of retinopathy in our study subjects.

     

Association study of candidate gene polymorphisms with amnestic mild cognitive impairment in a chinese population

To investigate the relationship between amnestic mild cognitive impairment (aMCI) and candidate gene polymorphisms in a Chinese population, 116 aMCI patients and 93 normal controls were recruited. Multi-dimensional neuropsychological tests were used to extensively assess the cognitive functions of the subjects. MassARRAY and iPLEX systems were used to measure candidate single nucleotide polymorohisms (SNPs) and analyse allelic, genotypic or haplotypic distributions. The scores of the neuropsychological tests were significantly lower for the aMCI patients than for the normal controls. The distributions of SNPs relating to the amyloid cascade hypothesis (TOMM40 rs157581 G and TOMM40 rs2075650 G), to the cholesterol metabolism hypothesis (ApoE rs429358 C, LDLR rs11668477 G and CH25H rs7091822 T and PLAU rs2227564 CT) and to the tau hypothesis (MAPT/STH rs242562 GG) in aMCI were significantly different than those in normal controls. Interactions were also found in aMCI amongst SNPs in LDLR rs11668477, PLAU rs2227564, and TOMM40 rs157581, between SNPs in TOMM40 rs157580 and BACE2 rs9975138. The study suggests that aMCI is characterised by memory impairment and associated with SNPs in three systems relating to the pathogenesis of AD-those of the amyloid cascade, tau and cholesterol metabolism pathways. Interactions were also observed between genes in the amyloid pathway and between the amyloid and cholesterol pathways.     

Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited

By studying the loci that contribute to human longevity, we aim to identify mechanisms that contribute to healthy aging. To identify such loci, we performed a genome-wide association study (GWAS) comparing 403 unrelated nonagenarians from long-living families included in the Leiden Longevity Study (LLS) and 1670 younger population controls. The strongest candidate SNPs from this GWAS have been analyzed in a meta-analysis of nonagenarian cases from the Rotterdam Study, Leiden 85-plus study, and Danish 1905 cohort. Only one of the 62 prioritized SNPs from the GWAS analysis (P<1×10(-4) ) showed genome-wide significance with survival into old age in the meta-analysis of 4149 nonagenarian cases and 7582 younger controls [OR=0.71 (95% CI 0.65-0.77), P=3.39 × 10(-17) ]. This SNP, rs2075650, is located in TOMM40 at chromosome 19q13.32 close to the apolipoprotein E (APOE) gene. Although there was only moderate linkage disequilibrium between rs2075650 and the ApoE ε4 defining SNP rs429358, we could not find an APOE-independent effect of rs2075650 on longevity, either in cross-sectional or in longitudinal analyses. As expected, rs429358 associated with metabolic phenotypes in the offspring of the nonagenarian cases from the LLS and their partners. In addition, we observed a novel association between this locus and serum levels of IGF-1 in women (P=0.005). In conclusion, the major locus determining familial longevity up to high age as detected by GWAS was marked by rs2075650, which tags the deleterious effects of the ApoE ε4 allele. No other major longevity locus was found.     

Peroxisome proliferator-activated receptor-gamma gene polymorphisms are not associated with osteonecrosis of the femoral head in the Korean population

Osteonecrosis of the femoral head (ONFH) is a multifactorial disease to which certain individuals are more at risk. Altered lipid metabolism is one of the major risk factors for osteonecrosis, especially corticosteroid therapy and alcoholism. Peroxisome Proliferator-Activated Receptor-gamma (PPARgamma) plays a crucial role in differentiation of mesenchymal cells to adipocytes, lipid homeostasis, and bone metabolism. To investigate the possible association between PPARgamma gene variants and susceptibility to ONFH, we genotyped three common polymorphisms (-796A > G, +34C > G[Pro12Ala], and +82466C > T[His477His]) in 448 ONFH patients and 336 control subjects. Genotypes, allele frequencies, and haplotypes of the polymorphisms in the complete set of patients as well as in subgroups by sex or etiology were not significantly different from those in the control group. This suggests that the examined polymorphisms and haplotypes of the PPARgamma gene are unlikely to be associated with susceptibility to ONFH.     

Development of a Melting Curve-Based Allele-Specific PCR of Apolipoprotein E (APOE) Genotyping Method for Genomic DNA,Guthrie Blood Spot,and Whole Blood

Genetic polymorphisms of apolipoprotein E (APOE) are associated with various health conditions and diseases, such as Alzheimer’s disease, cardiovascular diseases, type 2 diabetes, etc. Hence, genotyping of APOE has broad applications in biomedical research and clinical settings, particularly in the era of precision medicine. The study aimed to develop a convenient and accurate method with flexible throughput to genotype the APOE polymorphisms. A melting curve-based allele-specific PCR method was developed to genotype two single nucleotide polymorphisms (SNPs) of APOE, i.e. rs429358 at codon 112 and rs7412 at codon 158. These two SNPs determine the genotype of APOE2, E3, and E4. PCR-based Sanger sequencing was used as the reference method for APOE genotyping. A 100% concordance rate was obtained in 300 subjects between the melting curve-based allele-specific PCR method and the Sanger sequencing method. This method was applied to a genetic association analysis of APOE and schizophrenia consisting of 711 patients with schizophrenia and 665 control subjects from Taiwan. However, no significant differences in the allele and genotype frequencies were detected between these two groups. Further experiments showed that DNA dissolved from blood collected on Guthrie filter paper and total blood cell lysate without DNA extraction can be used in the melting curve-based allele-specific PCR method. Thus, we suggest that this is a fast, accurate and robust APOE genotyping method with a flexible throughput and suitable for DNA template from different preparations. This convenient method shall meet the different needs of various research and clinical laboratories.     

Polymorphisms in DNA Repair Gene and Susceptibility to Glioma: A Systematic Review and Meta-Analysis Based on 33 Studies with 15 SNPs in 9 Genes

At present, many publications have evaluated the correlation between the DNA repair gene polymorphisms and glioma susceptibility. However, the results remain inconclusive. The aim of this research is to exhaustively assess the association of genetic polymorphisms in DNA repair genes with glioma risk in human. Meta-analysis method was conducted, and 33 studies with 15 SNPs in 9 genes were included (12553 glioma cases and 17178 controls). Correlation strength was evaluated by odds ratio with a 95 % confidence interval. Rs1799782 T allele and rs25487A allele might bring about higher risk of glioma in Asian population. Rs1805377 G allele was an increased risk genetic factor of glioma. Asian carried with rs3212986 A allele was more likely to have glioma. Rs1800067 G allele was a risk factor of developing glioma. Carriers with rs12917 CC genotype in MGMT gene had higher risk of glioma in Caucasian than other non-CC genotype carriers. Carriers with rs1136410 T allele in PARP1 gene could more likely to develop glioma in Caucasian. This meta-analysis suggests that glioma susceptibility is associated with rs1799782 and rs25487 of X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1), rs1805377 of XRCC4, rs1800067 of excision repair cross-complementing rodent repair deficiency complementation group 4 (ERCC4) and rs3212986 of ERCC1 in Asian population, and rs12917 of O-6-methylguanine-DNA methyltransferase (MGMT) and rs1136410 of poly(ADP-ribose) polymerase 1 (PARP1) in Caucasian population.     

Lack of association between the polymorphisms of hypoxia-inducible factor 1A (HIF1A) gene and SLE susceptibility in a Chinese population

Hypoxia-inducible factor 1 (HIF-1) introduced the immune imbalance between Th17 and Treg cells, which may play an important role in the pathogenesis of systemic lupus erythematosus (SLE). The aim of the present study was to determine whether the HIF1A gene influences the susceptibility to SLE. A study on this relationship has not been conducted to date. A total of 3,793 subjects (1,497 SLE patients and 2,296 controls) were included in this study. The genotyping of five single-nucleotide polymorphisms (SNPs) (rs11549465, rs12434438, rs1957757, rs1951795, rs7143164) was determined by Sequenom MassARRAY technology. The statistical analysis was conducted using chi-square test. Odds ratio (OR) with 95 % confidence interval (CI) was calculated using unconditional logistic regression with adjustment of age and sex. The allele frequencies were not associated with the disease. No significant differences in genotype frequencies existed between the patients with SLE and the controls in all five SNPs. It is worth mentioning that the allele T at rs11549465, located at the exon sequence, revealed a trend but no significant difference towards the more frequent allele T in SLE than in controls (C versus T: OR?=?1.206, 95 % CI?=?0.972–1.495, p?=?0.088). The genotype effects of recessive, dominant, and codominant models were observed; however, no significant evidence for association was detected. Our findings suggest that the gene polymorphisms of HIF1A might not contribute to SLE susceptibility in the Chinese population. However, further studies are needed on an independent cohort from different genetic backgrounds to confirm HIF1A as an SLE genetic factor.