Ligation Detection Reaction Research Articles

S100A14 rs11548103 G>A polymorphism is associated with a decreased risk of esophageal cancer in a Chinese population.

ObjectiveIn China in 2009, esophageal cancer was the fifth most commonly diagnosed malignancy and the fourth leading cause of malignancy-related death. Accumulating evidence indicates that genetic factors might play an important role in esophageal squamous cell carcinoma (ESCC) carcinogenesis.Materials and MethodsIn total, we recruited 629 ESCC patients and 686 controls. Genetic variations in the S100A14, MLH1, SMAD7 and CCL22/MDC genes were measured using the ligation detection reaction method.ResultsWhen the S100A14 rs11548103 GG genotype was considered as the reference group, the GA genotype associated with decreased risk of ESCC (GA vs. GG: adjusted OR = 0.73, 95% CI = 0.57–0.93, p = 0.009). In the dominant model, GA/AA variants were associated with a significantly decreased risk of ESCC compared with the GG genotype (GA/AA vs. GG: adjusted OR = 0.76, 95% CI = 0.61–0.95, p = 0.018). Logistic regression analyses showed that the MLH1 rs1800734 C>T, SMAD7 rs12953717 C>T and CCL22/MDC rs4359426C>A polymorphisms were not associated with the risk of ESCC in any of the models tested.ConclusionsOur findings indicated that, in a Chinese population, rs11548103 might contribute to a decreased risk of ESCC. Further studies are need to confirm these data with results from a lager cohort and different ethnic origins.

PADI4 rs2240337 G>A polymorphism is associated with susceptibility of esophageal squamous cell carcinoma in a Chinese population.

BackgroundEsophageal cancer (EC) remains one of the major causes of cancer incidence and mortality worldwide. Genetic factors, such as single nucleotide polymorphisms (SNPs), may contribute to the carcinogenesis of EC.MethodsWe conducted a hospital based case-control study to evaluate the genetic susceptibility of SNPs on the development of EC. A total of 629 esophageal squamous cell carcinoma (ESCC) cases and 686 controls were enrolled for this study. Seven PADI4 SNPs were determined by ligation detection reaction method.ResultsOur findings suggested that the PADI4 rs2240337 GA/AA variants were significantly associated with decreased risk of ESCC. Haplotype PADI4 Ars2477137Crs1886302Grs11203366Grs16825533Grs2240337Ars1635564Ars1635562 and Crs2477137Trs1886302Grs11203366Ars1635564Grs2240337Crs1635564Trs1635562 polymorphism was correlated with decreased susceptibility to ESCC, while Crs2477137Trs1886302Ars11203366Ars1635564Grs2240337Ars1635564Ars1635562 was correlated with increased susceptibility of ESCC. Stratification analyses demonstrated that smoking significantly increased ESCC risk in PADI4 rs11203366 AG/AA, rs1886302 CC/CT, rs1635562 AT, rs1635564 CA and rs2477137 AC genotype. Alcohol drinking increased ESCC risk in PADI4 rs11203366 AG, rs1635562 AT, rs1635564 CA, rs2477137 AC, rs1886302 CT genotype. In younger cohort (<63 years), rs11203366 AA genotype was associated with increased risk of ESCC. PADI4 rs1886302 CC variant was associated with ESCC susceptibility in female cohort.ConclusionsOur study suggested that PADI4 rs2240337 G>A polymorphism may be correlated with individual susceptibility to ESCC. PADI4 rs11203366, rs1886302, rs1635562, rs1635564 and rs2477137 polymorphisms were implicated with altered susceptibility of ESCC based on sex, age, smoking status and alcohol consumption. However, larger studies among different ethnic populations and further experiments using genetically mutated cells or animals are warranted to verify our conclusion.

Design and validation of a DNA-microarray for phylogenetic analysis of bacterial communities in different oral samples and dental implants

The quali-quantitative characterization of the oral microbiota is crucial for an exhaustive knowledge of the oral ecology and the modifications of the microbial composition that occur during periodontal pathologies. In this study, we designed and validated a new phylogenetic DNA-microarray (OralArray) to quickly and reliably characterize the most representative bacterial groups that colonize the oral cavity. The OralArray is based on the Ligation Detection Reaction technology associated to Universal Arrays (LDR-UA), and includes 22 probe sets targeted to bacteria belonging to the phyla Firmicutes, Proteobacteria, Actinobacteria, Bacteroidetes, Fusobacteria, and Spirochaete. The tool is characterized by high specificity, sensitivity and reproducibility. The OralArray was successfully tested and validated on different oral samples (saliva, lingual plaque, supragingival plaque, and healing cap) collected from 10 healthy subjects. For each specimen, a microbial signature was obtained, and our results established the presence of an oral microbial profile specific for each subject. Moreover, the tool was applied to evaluate the efficacy of a disinfectant treatment on the healing caps before their usage. The OralArray is, thus, suitable to study the microbiota associated with various oral sites and to monitor changes arising from therapeutic treatments.

Association of the OAS3 rs1859330 G/A genetic polymorphism with severity of enterovirus-71 infection in Chinese Han children.

The 2'5'-oligoadenylate synthetase (OAS) is an interferon (IFN)-induced protein that plays an important role in the antiviral action of IFN, with OAS3 being one of the four OAS classes (OAS1, OAS2, OAS3, OASL). The effect of OAS on several infectious viral diseases has been reported; however, a study of the effect of OAS3 on enterovirus 71 (EV71) is lacking. The purpose of this study was to evaluate the association of the OAS3 rs1859330 G/A genetic polymorphism with susceptibility and severity of EV71 infection. We investigated 370 Chinese Han children with hand-foot-mouth disease (HFMD) (214 of which were mild cases while 156 were severe). An improved multiplex ligation detection reaction (iMLDR) technique was carried out to examine the genotype. The AA genotype distribution (p = 0.002) and A allele frequency (OR = 1.83, 95% CI 1.32-2.52, p < 0.001) of OAS3 rs1859330 in severe cases were significantly higher than in mild cases. When comparing the different genotypes in EV71-infected patients, there were statistical differences in relation to rash (p = 0.03), oral ulcers (p = 0.005), pathologic reflex (p = 0.003), WBC counts (p = 0.032), CRP (p = 0.024), BG concentrations (p = 0.029), ALT (p = 0.02), and EEG (p = 0.019). However, there were no differences in relation to age, gender, AST, CK-MB, CT/ MRI, as well as some symptoms and signs (e.g. duration of fever (days), headache, convulsions, consciousness disturbance, paralysis, sign of meningeal irritation). In the cerebrospinal fluid (CSF) of severe cases, there were no differences in the levels of white cells, protein, glucose, chloride, lymphocytes and monocytes between the different genotypes. The plasma levels of IFN-γ in EV71-infected patients were significantly higher than in the control group (p < 0.01). IFN-γ concentrations in severe cases were lower in A allele carriers (AA+GA) (118.5 ± 12.6pg/mL) than in GG homozygotes (152.6 ± 56.3pg/mL p < 0.05). These findings suggest that the OAS3 rs1859330 G/A genetic polymorphism is associated with the severity of EV-71 infection, and that the A allele is a risk factor for the development of severe EV71 infection.

Polymorphisms of VDR gene and risk of gastric cardiac adenocarcinoma in Chinese population.

Vitamin D receptor (VDR) gene polymorphisms have been reported to increase susceptibility to some malignant tumors, yet the effect on gastric cardiac adenocarcinoma susceptibility remains unknown. Here, we conducted a hospital-based case-control study to examine the correlation of single nucleotide polymorphisms of VDR rs2107301T>C, rs2228570C>T, rs1989969C>T and rs11568820 G>A and gastric cardiac adenocarcinoma susceptibility. A total 330 cases and 608 controls were enrolled in the study. Using ligation detection reaction, we found that the variant alleles of the four polymorphisms were not associated with risk of gastric cardiac adenocarcinoma. Further stratified analyses showed that there was an increased risk associated with VDR rs1989969 polymorphism among patients who were drinking or aged <60. The haplotypes VDR Trs2107301Trs2228570Crs1989969Grs11568820 reduced the susceptibility. This study demonstrated that VDR rs1989969 polymorphism was involved in the carcinogenesis of gastric cardiac adenocarcinoma, especially increased the risk in the younger and alcohol drinking Chinese population.

Significance of genetic polymorphisms in long non-coding RNA AC079767.4 in tuberculosis susceptibility and clinical phenotype in Western Chinese Han population

Recent studies have implicated long non-coding RNA, AC079767.4, as a highly susceptible gene in tuberculosis. The aim of the study was to preliminarily explore the possible association of single nucleotide polymorphisms (SNPs) in AC079767.4 gene with clinical phenotypes and TB susceptibility in Western Chinese Han population. The improved multiplex ligation detection reaction (iMLDR) method was employed to genotype 4 SNPs in AC079767.4 in 554 tuberculosis patients and 561 healthy individuals. In subgroup analysis, only the C allele for rs12477677 was associated with the decreased susceptibility to pulmonary TB with a p-value of 0.026, but p-value was 0.103 after Bonferroni correction. In total samples, haplotype [ACAC], representing four AC079767.4 variants, was found to slightly decrease TB risk (p = 0.045). Furthermore, patients with the CC genotype of rs12477677 were correlated with fewer occurrences of fever (p = 0.016), while patients carrying the T allele were associated with lower levels of ESR in the dominant model of rs1055229 (p = 0.021). For the first time, we reported the potential susceptibility and clinical traits of tuberculosis with lncRNA variants in the Western Han Chinese population. Our data indicate AC079767.4 polymorphisms may potentially act as novel biomarkers for tuberculosis diagnostic and therapeutic purposes.

Flap endonuclease-1 rs174538 G>A polymorphisms are associated with the risk of esophageal cancer in a Chinese population.

BackgroundEsophageal cancer has a high mortality rate, particularly in Asia, and there are obvious racial differences in regard to incidence. The purpose of our study was to assess the genetic susceptibility of functional single nucleotide polymorphisms in flap endonuclease‐1 (FEN1) in esophageal squamous cell carcinoma ESCC.MethodsClinical blood samples of 629 ESCC cases and 686 control samples were collected. The ligation detection reaction method was used to determine FEN 1 rs174538 G>A genotypes.ResultsA significantly decreased risk of ESCC was associated with FEN 1 rs174538 GA genotypes among patients under 63 years old.ConclusionsOur results suggest that functional polymorphism FEN 1 rs174538 G>A might affect personal susceptibility to ESCC. This result provides a solid theoretical foundation for further clinical study using larger sample sizes.

Association of Toll-like receptor 3 gene polymorphism with the severity of enterovirus 71 infection in Chinese children.

Enterovirus 71 (EV71) infection has become one of the major threats to children globally in recent years. Toll-like receptor 3 (TLR3) plays an essential role in host defense against EV71 infection. This study was designed to assess the possible association between the TLR3c.1377C/T polymorphism and disease severity in Chinese children with EV71 infection. The TLR3c.1377C/T gene polymorphism was identified in EV71-infected patients (n = 177), including mild cases (n = 99) and severe cases (n = 78) as well as healthy controls (n = 225), using improved multiplex ligation detection reaction (iMLDR) technology. Serum levels of IFN-γ and IL-4 were measured using enzyme-linked immunosorbent assays. The presence of the TT genotype (p = 0.030) and the T allele (OR, 1.8; 95% CI, 1.2-2.8; p = 0.010) was significantly more frequent in severe cases. The plasma levels of IFN-γ and the IFN-γ/IL-4 ratio were significantly lower with the TT (102.0 ± 24.2 pg/mL, p < 0.01 and 14.2 ± 2.8, p < 0.001) and CT genotypes (114.1 ± 26.2 pg/mL, p < 0.05 and 18.0 ± 3.1, p < 0.001) than with the CC genotype (135.5 ± 36.8 pg/mL and 24.9 ± 4.7), but the plasma levels of IL-4 with the TT (7.3 ± 1.7 pg/mL, p < 0.01) and CT genotypes (6.4 ± 1.3 pg/mL, p < 0.05) were significantly higher than with the CC genotype (5.5 ±1.3 pg/mL). These findings suggest that the TLR3c.1377T allele is associated with susceptibility to severe EV71 infection in Chinese children.

Tagging polymorphisms of methyl-CpG binding domain 4 and gastric cardiac adenocarcinoma risk in a Chinese population.

Potential effects of genetic factors on carcinogenesis of gastric cardiac adenocarcinoma (GCA) may exist. The present experiment specifically evaluated the genetic influence of single nucleotide in methyl-CpG binding domain 4 (MBD4) on GCA tumorigenesis. A case-control experiment based on hospital recruited 330 GCA patients and 608 non-cancer patients was carried out. We employed ligation detection reaction method to detect the genotypes. The results revealed that MBD4 rs3138373, rs2005618, and rs3138355 mutations had no significant association with the risk of GCA. However, a lower risk of GCA presented in male patients who carried the MBD4 rs3138355 G>A polymorphic loci by the stratified analyses. In general, The MBD4 gene polymorphism could not influence GCA hereditary predisposition. Nevertheless, whether the finding learned from our experiment could apply to other ethnic groups will remain vague until future multicenter studies further test and verify our conclusions.

Detection of nucleotide-specific CRISPR/Cas9 modified alleles using multiplex ligation detection.

CRISPR/Cas9 genome-editing has emerged as a powerful tool to create mutant alleles in model organisms. However, the precision with which these mutations are created has introduced a new set of complications for genotyping and colony management. Traditional gene-targeting approaches in many experimental organisms incorporated exogenous DNA and/or allele specific sequence that allow for genotyping strategies based on binary readout of PCR product amplification and size selection. In contrast, alleles created by non-homologous end-joining (NHEJ) repair of double-stranded DNA breaks generated by Cas9 are much less amenable to such strategies. Here we describe a novel genotyping strategy that is cost effective, sequence specific and allows for accurate and efficient multiplexing of small insertion-deletions and single-nucleotide variants characteristic of CRISPR/Cas9 edited alleles. We show that ligation detection reaction (LDR) can be used to generate products that are sequence specific and uniquely detected by product size and/or fluorescent tags. The method works independently of the model organism and will be useful for colony management as mutant alleles differing by a few nucleotides become more prevalent in experimental animal colonies.

The COMT rs4680 polymorphism and suicide attempt in rural Shandong, China.

Suicide attempt is a major public health problem and are associated with genetic factors. This paired case-control study examined the association between the COMT gene rs4680 polymorphism and suicide attempts. A case-control study of 369 (117 men, 31.7%; mean age=44.1±13.3 years) suicide attempters and an equal number of controls without a lifetime history of suicide attempt matched on sex, age, and residence was carried out in rural Shandong, Eastern China. Demographics and psychiatric history were obtained through face-to-face interviews. Blood samples were collected during interviews and the COMT gene rs4680 polymorphism was analyzed using the ligation detection reaction method. The G/G genotype was significantly more prevalent in female suicide attempters than their matched controls. Conditional logistic regression showed that the G/G genotype was significantly associated with an increased risk of suicide attempts only for women (odds ratio=2.3; 95% confidence interval: 1.2-4.2). The findings support an association between the COMT gene rs4680 polymorphism and suicide attempts only in women. Further research with larger samples is needed to explore the interactions of the COMT gene rs4680 polymorphism and sex and psychiatric disorders on suicide attempts.

Association of genetic polymorphisms around the LIN28B gene and idiopathic central precocious puberty risks among Chinese girls.

Genome-wide association studies have identified rs314276, rs314263, rs7759938, and rs314280 in or near the LIN28B gene as associated with age at menarche. To date, the effect of polymorphisms in this gene on idiopathic central precocious puberty (ICPP) in Chinese girls have not been reported. The aim of this study was to evaluate the association of the four loci with ICPP in Chinese girls. In this study, we conducted a case-control study including 502 girls with ICPP and 489 controls. Four single-nucleotide polymorphisms (SNPs) were genotyped in both groups using an improved multiplex ligation detection reaction (iMLDR) technique. Of the four SNPs of the LIN28B analyzed, three SNPs, rs314276, rs7759938, and rs314280, were associated with ICPP risk at P < 0.05. The association of rs314276, however, was no longer significant after adjustment for multiple testing. Compared with rs7759938 TT or TC genotype, decreased ICPP risk was associated with CC (OR = 0.527, 95% CI: 0.329-0.843) genotype (P = 0.008). Compared with rs314280 GG or GA genotype, decreased ICPP risk was associated with minor allele carrier (AA) genotype (OR = 0.538, 95% CI: 0.337-0.858, P = 0.009). The two identified variants showed the same association signals for ICPP. In conclusion, common genetic variations (rs7759938 and rs314280) of LIN28B may contribute to ICPP susceptibility in Chinese girls.

Gene Polymorphisms in the RANKL/RANK/OPG Pathway Are Associated with Type 2 Diabetes Mellitus in Southern Han Chinese Women.

Receptor activator of nuclear factor-kappa B ligand (RANKL), its receptor activator of nuclear factor-kappa B (RANK), and decoy receptor osteoprotegerin (OPG) are three major proteins of the RANKL/RANK/OPG signaling pathway encoded by TNFSF11, TNFRSF11A, and TNFRSF11B, respectively. This pathway plays a critical role in bone remodeling and may have a role in the pathogenesis of type 2 diabetes mellitus (T2DM). The aim of this study was to investigate the relationship between gene polymorphisms in the RANKL/RANK/OPG pathway and T2DM in Southern Han Chinese women. A total of 1233 participants, including 514 T2DM patients and 719 healthy control subjects, were enrolled in this case-control study. Twenty-one single-nucleotide polymorphisms (SNPs) of TNFSF11, TNFRSF11A, and TNFRSF11B were genotyped using an improved multiplex ligation detection reaction technique. Two SNPs of TNFRSF11B (rs11573819 and rs2073618) were significantly associated with T2DM (p = 0.04 and p = 0.009, respectively). Subjects with the GA genotype of rs11573819 had a lower risk of T2DM (odds ratio [OR] = 0.67, 95% confidence interval [CI] = 0.51-0.88, p = 0.005) compared with subjects with the GG genotype. The GG genotype of rs2073618 was associated with increased risk for T2DM (OR = 1.94, 95% CI = 1.14-3.30, p = 0.01) compared with the CC genotype. This study suggests that TNFRSF11B but not TNFSF11 and TNFRSF11A genetic polymorphisms are associated with T2DM in Southern Han Chinese women. These findings provide preliminary support for the potential role of the RANKL/RANK/OPG pathway in T2DM.

Functional Analysis of SNPs in the ERCC5 Promoter in Advanced Colorectal Cancer Patients Treated With Oxaliplatin-Based Chemotherapy.

The promoter is the center for regulation of gene transcription due to containing numerous transcription factor binding sites. The aim of the study was to determine whether genetic variations at excision repair cross complementation group 5 (ERCC5) promoter could affect transcription factor binding and whether such single nucleotide polymorphism (SNP)-dependent binding could affect gene expression, drug response, and clinical outcome.A total of 170 patients who were cytologically or histologically confirmed with advanced colorectal cancer (CRC), at least 1 measurable lesion, and underwent oxaliplatin-based chemotherapy were studied. The polymerase chain reaction–ligation detection reaction (PCR-LDR) was used to analyze SNPs. The reporter gene assay system and electrophoretic mobility shift assays (EMSA) were performed to investigate the effect of SNPs on the ERCC5 promoter activity and DNA-binding activity, respectively. The mRNA and protein expression of ERCC5 in tumor tissues of colorectal cancer patients with different genotypes were detected by real-time PCR and western blot, respectively.Both −763A and −763G allele had nuclear protein-binding ability. +25A allele did not show any nuclear protein-binding ability, whereas +25G allele did. The relative luciferase activity of the −763A/+25G haplotype was significantly higher than other 3 haplotypes (P < 0.05). The expression level of ERCC5 mRNA and protein was significantly higher in tumor tissues with −763AA+25GG genotype combination than that with −763GG+25AA genotype combination (P < 0.05, respectively). Allelic variants (−763AA vs −763AG or –763GG, +25GG versus +25AG or +25AA) were significantly associated with shorter progression-free survival (PFS) and overall survival (OS) (P < 0.05, respectively). At multivariate analysis, patients with risk genotypes (−763AA or +25GG genotype) demonstrated a significantly increasing risk of progression (P = 0.01) or worse OS (P = 0.001).The ERCC5 promoter polymorphisms at −763 and +25 may be important functional variants and predictors of clinical outcome of CRC patients who received oxaliplatin chemotherapy.

No Significant Effect of ASAP1 Gene Variants on the Susceptibility to Tuberculosis in Chinese Population.

Recent studies have proposed that the ASAP1 gene participates in regulating the adaptive immune response to Mycobacterium tuberculosis infection. A GWAS study has reported that ASAP1 polymorphisms (rs4733781 and rs10956514) were associated with the risk of tuberculosis (TB) in Russians. But due to population heterogeneity, different races would have different causative polymorphisms, and the aim of this study was to investigate the association between single nucleotide polymorphisms (SNPs) of the ASAP1 gene and TB risk in Chinese population.A total of 7 SNPs in the ASAP1 gene were genotyped in 1115 Western Chinese Han and 914 Tibetan population using an improved multiplex ligation detection reaction (iMLDR) method. The associations of SNPs with TB risk and clinical phenotypes were determined based on the distributions of allelic frequencies and different genetic models. A meta-analysis was carried out to further assess the relationship between ASAP1 polymorphism and TB risk.Statistical comparisons of cases and controls after correction for multiple testing did not yield any significant associations with the risk of TB via analyses of a single locus, haplotype, and subgroup differences. Meta-analysis showed no evidence supporting association between rs10956514 and overall risk for TB. Subsequent analysis referring to the genotypes of SNPs in relationship to clinical phenotypes identified that rs4236749 was associated with different serum C-reactive protein levels, suggesting a role of this locus in influencing the inflammatory state of Western Chinese Han patients with TB.Our present data revealed that ASAP1 polymorphisms are unlikely to confer susceptibility to TB in the Western Chinese Han and Tibetan populations, which challenges the promising roles of the ASAP1 gene in the development of TB and highlights the importance of validating the association findings across ethnicities.

Forkhead box A1 (FOXA1) tagging polymorphisms and esophageal cancer risk in a Chinese population: a fine-mapping study

Esophageal cancer was the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related death in China in 2009. Esophageal squamous cell carcinoma (ESCC) accounts for more than 90% of esophageal cancers. Besides environmental risk factors, genetic factors such as single-nucleotide polymorphisms (SNPs) play an important role in ESCC carcinogenesis. We performed a hospital-based case–control study to evaluate the Forkhead-box protein A1 (FOXA1) rs12894364 C > T, rs2145146 C > A and rs7144658 T > C tag SNPs in the risk of developing ESCC. We recruited 629 ESCC cases and 686 controls. Genotypes were determined using ligation detection reaction. Logistic regression analyses revealed that the three FOXA1 SNPs were not associated with ESCC risk. However, there was significantly decreased ESCC risk associated with the FOXA1 rs12894364 C > T and rs2145146 C > A polymorphisms among older patients. There was significantly increased ESCC risk associated with the FOXA1 rs7144658 T > C polymorphism among male patients. This study demonstrates an association between FOXA1 polymorphisms and ESCC susceptibility. Additional larger studies are required to confirm our findings.

Identification of Haplotype Tag Single-Nucleotide Polymorphisms within the PPAR Family Genes and Their Clinical Relevance in Patients with Major Trauma.

Background: Peroxisome proliferator-activated receptors (PPARs) play important roles in the development of inflammatory diseases and sepsis. Recently, genetic variants of PPARs genes have been widely studied in some inflammatory diseases. However, the association between PPAR family of genes polymorphisms and sepsis risk in trauma patients was little known. Methods: SNPs were selected from the PPARs genes through constructing haplotype blocks and genotyped by the improved multiplex ligation detection reaction (iMLDR) method. The association between the selected SNPs and the risk of sepsis and multiple organ dysfunction (MOD) scores was evaluated in 734 trauma patients. In addition, tumor necrosis factor α (TNFα) production of peripheral blood leukocytes was also analyzed after lipopolysaccharide (LPS) stimulation. Results: Our results revealed that there were significant associations between the rs10865710 polymorphism and the risk of sepsis and MOD scores in Chinese Han trauma patients. Further, we found that the level of TNFα production was higher in patients with the rs10865710 G allele compared to those with the variant C allele. Conclusions: The rs10865710 polymorphism in the PPARγ gene might be used to assess the risk of sepsis and multiple organ dysfunction syndrome (MODS) in trauma patients.

Single nucleotide polymorphisms of TNFAIP3 are associated with systemic lupus erythematosus in Han Chinese population.

The polymorphisms of tumour necrosis factor alpha-induced protein 3 (TNFAIP3) have been found to associate with several autoimmune diseases. This study aimed to explore the association of single nucleotide polymorphisms (SNPs) of TNFAIP3 gene with systemic lupus erythematosus (SLE) in Han Chinese. Thirty-two SNPs were genotyped in 284 patients with SLE and 630 controls using the ligation detection reaction (LDR) method. The quality control steps and statistical analyses were performed using the PLINK 1.07 package and HAPLOVIEW software. We found that 13 SNPs in TNFAIP3 showed significant association with SLE (P < 1.85 × 10(-3)), and all of them were in high linkage disequilibrium (LD). After conditioning on the SNP rs2230926, other 12 SNPs did not show association (P > 0.27). All 13 SNPs showed most significant association in the dominant model. In haplotype analysis, a long risk SNP haplotype (GCCCGTGTCATGG) showed most significant association (P = 1.00 × 10(-4)). In conclusion, our data suggest that TNFAIP3 is a susceptible gene for SLE in the Han Chinese population.

Abstract WP394: The Proteasome Subunit α Type 6 Rs1048990 Contributes To The Risk Of Ischemic Stroke And Its Subtypes: New Data And Meta-analysis

Background and purpose: The proteasome subunit α type 6 (PSMA6) is an important proteolytic protein regulating the expression of genes involved in inflammation. Recently, a functional polymorphism rs1048990, located in PSMA6 , has been reported with the susceptibility to ischemic stroke (IS) in several ethnic cohorts, but the results were inconsistent. Moreover, it still lacks the data in Asian. The purpose of the present study was to determine whether this polymorphism confers significant risk to IS in a Chinese population. Methods: A total of 1102 IS cases and 975 healthy controls were analyzed in our study. We genotyped rs1048990 with ligation detection reaction (LDR) method and then performed a meta-analysis. Results: Significant association between rs1048990 in PSMA6 and ischemic stroke was observed in all comparison models (genotype, p =0.016; allele, p =0.004; CG+GG vs. CC, adjusted p =0.006; GG vs. CG+CC, adjusted p =0.038). Further stratification for stroke subtype, similar differences also can be found in large artery atherosclerosis and cardioembolism, but not small vessel occlusion. In addition, in the analysis of genotype-phenotype correlation, the onset ages of allele-G carriers have a trend to be older than non-carriers’ ( p &lt;0.001). In the meta-analysis, there is no significant difference between rs1048990 and ischemic stroke, for the great discrepancy of the genotype composition between Caucasian and Chinese. Conclusion: Our study suggests that rs1048990 contributes to the risk of IS and its subtypes in Chinese population, but these associations may vary in different ethnic populations.

Polymorphism of HDAC9 Gene Is Associated with Increased Risk of Acute Coronary Syndrome in Chinese Han Population.

Recent genome-wide association studies (GWAS) have indicated an association of histone deacetylase 9 (HDAC9) genetic variant with large-vessel stroke and coronary artery disease, among the European population. However, whether HDAC9 gene is associated with an increased susceptibility to acute coronary syndrome (ACS) in Chinese Han population is not known. A total of 472 patients, including patients with ACS (N = 309), and those with chest pain syndrome (controls, N = 163) were enrolled. Genotyping for HDAC9 gene was performed using the ligation detection reaction assay. A series of statistical analyses were performed to investigate the correlation between HDAC9 gene SNPs and the susceptibility to ACS. The results revealed a significant association of rs2240419 with ACS risk in which the A allele (P = 0.047) and the A allele carriers (AA + AG) (P = 0.037) were more likely to be in ACS group as compared to those in the control group. None of two other SNPs, rs2389995 and rs2107595, were significantly associated with ACS risk (P > 0.05). Logistic regression analyses further revealed an increased risk for ACS in A allele carrier among rs2240419 genotypes, as compared to those with GG homozygotes (odds ratio: 1.869, 95% CI 1.143, 3.056, P = 0.013). A significant correlation between rs2240419 polymorphism of HDAC9 gene and the susceptibility to ACS in Chinese Han population was observed in this study.