Polymerase Chain Reaction-ligation Detection Reaction Research Articles

Association of Nucleostemin Polymorphisms with Chronic Hepatitis B Virus Infection in Chinese Han Population.

Background: Chronic hepatitis B virus infection (CHB) is a common infectious disease that poses a global economic and health burden due to its high morbidity and mortality. Studies have demonstrated that host genetic factors play critical roles in the susceptibility and outcome of CHB. Aims: In this study, we aimed to assess the potential role of genetic variants of the nucleostemin (NS) gene with respect to CHB susceptibility. Materials and Methods: Four single nucleotide polymorphisms (SNPs) in the NS gene were genotyped in 446 patients with CHB and 399 healthy controls all of Chinese Han origin using the polymerase chain reaction-ligation detection reaction method. Results: The results showed that the three SNPs, rs3733039, rs1866268, and rs11177, were significantly associated with CHB. After a Bonferroni correction, the positive association of the rs3733039 SNP with CHB remained significant. Further analyses based on gender demonstrated that these SNPs are associated with CHB in both the female and male subgroups. After correction for multiple comparisons, all three SNPs in the female group were associated with CHB, whereas only the rs1866268 SNP in the male group was associated with CHB. Haplotype analysis showed that the C-C-G and T-T-T haplotypes in the block consisting of rs3733039-rs1866268-rs11177 were significantly associated with CHB. Conclusion: Our study demonstrated a genetic association between SNPs in the NS gene and the risk of CHB in the Chinese Han population for the first time. Thus, variations in the NS gene might serve as potential genetic biomarkers of CHB.

Association of IGF1 single-nucleotide polymorphisms with myopia in Chinese children

PurposeTo investigate the association between insulin-like growth factor 1 (IGF1) single-nucleotide polymorphisms (SNPs) and myopia in a young Chinese population.MethodsA total of 654 Chinese children aged 6–13 years from one primary school participated in our study and underwent a series of comprehensive ocular examinations, including cycloplegic refraction and measurements of axial length. Myopia was defined as a spherical equivalence (SE) ≤ −0.5 D in the worse eye. In total, six tagging SNPs of IGF1 were genotyped using the PCR-LDR (Polymerase Chain Reaction-Ligation Detection Reaction) method. We tested four different genetic modes (the allele, dominant, recessive, and additive models) of these SNPs and used multivariate logistic regression to calculate the effect of SNPs on myopia. In addition, we conducted a haplotype analysis with a variable-sized slide-window strategy.ResultsOverall, 281 myopic children and 373 non-myopic controls were included in the analysis. The SNP rs2162679 showed a statistical difference between the two groups in both the allele (p = 0.0474) and additive (p = 0.0497) models. After adjusting for age and gender, children with the genotype AA in the SNP rs2162679 had a higher risk of myopia than those with the genotype GG (OR = 2.219, 95% CI [1.218–4.039], p = 0.009). All haplotypes that varied significantly between the two groups contained the SNP rs2162679, and the four-SNP window rs5742653–rs2162679 had the lowest p value (Chi square = 5.768, p = 0.0163). However, after permutation tests, none of the associations remained statistically significant.ConclusionThe SNP rs2162679 in IGF1 was associated with myopia in a young Chinese population. The G allele in the SNP rs2162679 may protect against myopia.

Influence of miRNA Gene Polymorphism on Recurrence and Age at Onset of Ischemic Stroke in a Chinese Han Population.

Polymorphisms in microRNAs (miRNAs) are associated with ischemic stroke occurrence and traditional risk factors for ischemic stroke such as atherosclerosis, hypertension, hyperlipidemia, and diabetes. However, few studies have examined recurrent ischemic stroke as an outcome. Thus, the aim of our study was to examine association of miRNA gene polymorphisms (namely, miR-126 rs4636297, miR-149 rs2292832, miR-124 rs531564, miR-499 rs3746444, miR-143 rs12655723, and miR-122 rs17669) with recurrence of ischemic stroke. miRNA gene polymorphisms were genotyped using the polymerase chain reaction-ligation detection reaction (PCR-LDR) method in 657 patients with ischemic stroke. Association of miRNA polymorphisms with prognosis outcomes was examined by the Kaplan-Meier method, log-rank test, and Cox proportional hazards models. miR-122 rs17669 was significantly associated with recurrence risk of ischemic stroke under the recessive model. Cox regression analysis showed that the CC genotype of rs17669 was associated with an increased risk of 1.9-fold for stroke recurrence (hazard ratio = 1.879; 95% confidence interval = 1.182-2.985; P = 0.008). Further, this effect was more evident among the non-drinker and male subgroups. We found no difference in risk of recurrent ischemic stroke among the other five miRNA polymorphisms. Furthermore, we identified a significant association between the miR-149 rs2292832 polymorphism and age at onset of first-ever stroke. Altogether, miR-122 rs17669 is a significant predictor for the risk of recurrent stroke, independent of traditional risk factors.

The Association between Epidermal Growth Factor Receptor Single Nucleotide Polymorphisms and Radiochemotherapy Response in Cervical Cancer.

Emerging data reveal that epidermal growth factor receptor (EGFR) single nucleotide polymorphisms (SNPs) can act as efficacy indicators for tumor treatment. Here, the association between EGFR R497K (rs11543848) and -216G/T (rs712829) SNPs and radiochemotherapy response in cervical cancer was investigated. EGFR R497K and -216G/T genotypes were analyzed by polymerase chain reaction-ligation detection reaction in 196 cervical cancer patients receiving radiotherapy alone, or in combination with chemotherapy. Compared with the 497G/G genotype, the A/A genotype significantly increased sensitivity to radiochemotherapy treatment (adjusted OR = 0.244, 95% CI = 0.087-0.680). Sensitivity to radiochemotherapy was not significantly different in carriers of the 'T' allele than that measured for the -216G/G genotype (adjusted OR = 2.412, 95% CI = 0.856-6.979). Additionally, the 497A/A genotype conferred a reduced risk of recurrence or metastasis than did the G/G genotype (adjusted OR = 0.248, 95% CI = 0.078-0.786, P <0.05). Moreover, carriers of the 'T' allele did not have significantly modified risk of recurrence or metastasis compared with those with the -216G/G genotype (adjusted OR = 1.027, 95% CI = 0.324-3.253). Multivariate analysis revealed an association between clinical stage and treatment response (adjusted OR = 3.575, 95% CI = 1.662-7.692) and between age and the risk of recurrence or metastasis (adjusted OR = 0.319, 95% CI = 0.148-0.691). Our results show that, in patients with cervical cancer, the R497K polymorphism is correlated with treatment response and the risk of recurrence or metastasis. The R497K SNP might be a genetic marker for prediction of radiochemotherapy response and the risk of recurrence and/or metastasis in patients with cervical cancer.

Association between 12p13 Polymorphisms and Ischemic Stroke in Asian Populations: New Evidence from a Case-Control Study and a Meta-Analysis.

A genome-wide association study first reported the association between ischemic stroke risk and two polymorphisms on chromosome 12p13: rs12425791 and rs11833579. Since then, a series of studies have investigated the association of these two polymorphisms with stroke risk, but the results were inconsistent even in Asian populations. Thus, we carried out a case-control study to uncover the potential relationship, and then conducted a meta-analysis to further address the issue. 540 ischemic stroke patients and 540 unrelated controls were enrolled in the case-control study. Genotyping was accomplished by polymerase chain reaction-ligation detection reaction. The meta-analysis was conducted by combining our study with previous published data. In our case-control study, the significant association was observed between ischemic stroke and rs12425791 (AG vs. GG: OR = 1.32, P < 0.05) but not rs11833579. When pooled with previous studies, the significant relationship of rs12425791 with ischemic stroke was found (A vs. G: OR = 1.07, P < 0.05; AA + AG vs. GG: OR = 1.10, P < 0.05) in Asian populations, as well as in subgroup analysis. A correlation approachingsignificance was identified between ischemic stroke risk and rs11833579 (AA + AG vs. GG: OR = 1.06, P = 0.05). New evidence from this case-control study and meta-analysis indicates that 12p13 rs12425791/rs11833579 polymorphisms are associated with ischemic stroke susceptibility in Asian populations.

Association of IL-10-1082A/G Polymorphism with Ischemic Stroke: Evidence from a Case-Control Study to an Updated Meta-Analysis.

Interleukin-10 (IL-10) plays a vital part in the pathophysiology of vascular inflammation. Several studies have investigated the potential association between the IL-10-1082A/G polymorphism and the risk of ischemic stroke where the inflammatory process is involved, but the conclusions have been inconsistent. Three hundred eighty-six ischemic stroke patients and 386 healthy controls were recruited in the study. Genotyping was conducted by using the polymerase chain reaction-ligation detection reaction method. A meta-analysis was then performed by pooling our data with previous published studies. In our case-control study, a lack of association was revealed between IL-10-1082A/G and ischemic stroke (p > 0.05). When combined with previous studies, however, a significant relationship between IL-10-1082A/G and ischemic stroke risk was found (G vs. A: OR = 0.73, 95% CI = 0.60-0.88, p < 0.01; GG vs. AA: OR = 0.61, 95% CI = 0.49-0.76, p < 0.01; GG+AG vs. AA: OR = 0.70, 95% CI = 0.54-0.91, p < 0.01; GG vs. AG+AA: OR = 0.68, 95% CI = 0.52-0.89, p < 0.01), as well as in subgroup analyses. Sensitivity analysis and publication bias assessment supported the reliability of the results from the meta-analysis. Evidence from a case-control study to an updated meta-analysis suggests that the IL-10-1082A/G polymorphism is associated with ischemic stroke susceptibility.

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.

Genetic variants of mannose-binding lectin 2 gene influence progression and prognosis of patients with hepatitis B virus infection in China

Mannose-binding lectin (MBL) is a member of the calcium-dependent collectin family involved in the innate immune system that mediates phagocytosis and activates complement by binding to carbohydrate motifs. We studied allele and haplotype frequencies of -221C/G and codon 54G/A in MBL2 gene to reveal their relationship with the developing and progression of hepatitis B virus (HBV)-related liver diseases. This study was performed in 171 healthy controls, 133 chronic hepatitis B (CHB) patients, 97 patients with HBV-related liver cirrhosis (LC) and 334 HBV-related hepatocellular carcinoma (HCC) patients. The genotypes of these two polymorphisms in these subjects were detected using polymerase chain reaction-ligation detection reaction (PCR-LDR) method. Stratification analyses by clinical characteristics and survival analysis of HCC patients were also performed according to their genotypes. The genotype and allele frequencies at codon 54 manifested a significant difference between healthy controls and patients with progressive HBV-related liver diseases, especially liver cirrhosis. Allele A appeared to have protective effect from developing LC and HCC compared with G allele. The percentages of the patients with G allele at -221C/G increased in HBV-related disease groups. When combined together as a haplotype, lower haplotype AC frequency was associated with a decreased risk for the progression of HBV-related liver diseases and HCC developing. Furthermore, HCC patients with G allele at codon 54 showed to have better survival than those with A allele. These results indicated that polymorphisms in MBL2 gene may influence susceptibility, progression and prognosis of HBV-related liver diseases.

The MTHFR C677T Polymorphism and Risk of Intracerebral Hemorrhage in a Chinese Han Population.

BackgroundMethylenetetrahydrofolate reductase (MTHFR) C677T polymorphism has been speculated to be and extensively investigated as a risk factor for various vascular diseases, including intracerebral hemorrhage (ICH). However, results from published studies regarding the role of C677T polymorphism in ICH risk in Chinese populations were contradictory rather than conclusive.Material/MethodsIn this study, a total of 180 ICH patients and 180 matched controls of Chinese Han ethnicity were enrolled. The MTHFR C677T polymorphism was genotyped by polymerase chain reaction-ligation detection reaction (PCR-LDR). A meta-analysis was conducted by combining our data with previous relevant studies in Chinese populations.ResultsIn our case-control study, similar allele frequency (p=0.492) and genotype distribution (p=0.748) of MTHFR C677T polymorphism were detected between ICH patients and controls. Further analysis based on hematoma location did not show a significant association. When combined with previous studies, however, C677T polymorphism was found to be significantly associated with an increased risk for ICH in Chinese populations (recessive model: OR=1.57, 95%CI=1.29–1.91). When focusing on the Han ethnicity, carriers of the TT genotype had an increased risk of ICH (recessive model: OR=1.36, 95%CI=1.05–1.75).ConclusionsIn this case-control study we did not observe that the MTHFR C677T polymorphism was associated with ICH risk in people of Chinese Han ethnicity. However, when combined with previous published studies, a significant association of C677T polymorphism with an increased risk of ICH was detected in Chinese populations, and also in the subgroup analysis focusing on Han ethnicity.

MMP-9 gene polymorphisms (rs3918242, rs3918254 and rs4810482) and the risk of psoriasis vulgaris: No evidence for associations in a Chinese Han population

Several previous studies including one of them co-authored by our group have revealed that serum and psoriatic plaque expression of matrix metalloproteinase-9 (MMP-9) was significantly upregulated in psoriasis. The aim of this study was to investigate the association of three single nucleotide polymorphisms (SNPs) and haplotypes of MMP-9 (rs3918242, rs3918254 and rs4810482) with psoriasis vulgaris in a Chinese Han population. The serum levels of MMP-9 in 245 psoriasis vulgaris cases and 256 healthy controls were assessed using ELSA kits, and the three SNPs were genotyped using polymerase chain reaction–ligation detection reaction (PCR-LDR) method. Four haplotypes based on the three SNPs were also analyzed. Our study showed that the serum MMP-9 levels in patients with psoriasis vulgaris were significantly higher than that in controls (P<0.05). However, the three SNPs were not significantly associated with psoriasis vulgaris susceptibility (all P>0.05). Similar results were found in further subgroup analysis based on gender, age of onset, family history, and serum MMP-9 levels, except that a protective effect of psoriasis vulgaris was detected among female subjects with the CT genotype of rs3918254 (OR=0.47, 95% CI=0.23-0.96, P=0.038), but this association did not survive after Bonferroni correction (Padj=0.076). The haplotype analysis also failed to show any association with psoriasis vulgaris. We found no evidence for the association between the MMP-9 polymorphisms and psoriasis vulgaris susceptibility in a Chinese Han population.

Genetic Variants of IκB Kinase β (IKBKB) and Polymerase β (POLB) Were Not Associated with Systemic Lupus Erythematosus Risk in a Chinese Han Population.

A previous large-scale replication study validation of a genome wide association study (GWAS) identified IκB kinase β (IKBKB) single nucleotide polymorphisms (SNPs) as a risk factor associated with systemic lupus erythematosus (SLE) in a Chinese Han population. IKBKB SNPs were associated with polymerase β (POLB) SNPs and reduced POLB expression, and this was proposed to be an underlying cause of human SLE development. In the current case-control study, we evaluated IKBKB (rs12676482 and rs2272733) and POLB (rs3136717 and rs3136744) SNPs in 946 SLE patients and 961 healthy controls. We investigated the possible association of these four SNPs with SLE in a Chinese Han population using the polymerase chain reaction-ligation detection reaction (PCR-LDR) technique. The differences in the frequencies of the four SNP alleles and the genotypes and haplotypes of the POLB polymorphisms were statistically insignificant when the SLE patients were compared with the controls in the Chinese Han population enrolled in this study (all, p ˃ 0.05). Furthermore, no associations were detected using different genetic models (additive, dominant, and recessive; all, p ˃ 0.05). Our findings indicate that the IKBKB (rs12676482 and rs2272733) and POLB (rs3136717, rs3136744) SNPs confer no genetic predisposition to SLE risk in this Chinese Han population.

The association of APOC4 polymorphisms with premature coronary artery disease in a Chinese Han population.

BackgroundHypercholesterolemia arising from abnormal lipid metabolism is one of the critical risk factors for coronary artery disease (CAD), however the roles of genetic variants in lipid metabolism-related genes on premature CAD (≤60 years old) development still require further investigation. We herein genotyped four single nucleotide polymorphisms (SNPs) in lipid metabolism-related genes (rs1132899 and rs5167 in APOC4, rs1801693 and rs7765781 in LPA), aimed to shed light on the influence of these SNPs on individual susceptibility to early-onset CAD.MethodsGenotyping of the four SNPs (rs1132899, rs5167, rs1801693 and rs7765781) was performed in 224 premature CAD cases and 297 control subjects (≤60 years old) using polymerase chain reaction-ligation detection reaction (PCR–LDR) method. The association of these SNPs with premature CAD was performed with SPSS software.ResultsMultivariate logistic regression analysis showed that C allele (OR = 1.50, P = 0.027) and CC genotype (OR = 2.84, P = 0.022) of APOC4 rs1132899 were associated with increased premature CAD risk, while the other three SNPs had no significant effect. Further stratified analysis uncovered a more evident association with the risk of premature CAD among male subjects (C allele, OR = 1.65, and CC genotype, OR = 3.33).ConclusionsOur data provides the first evidence that APOC4 rs1132899 polymorphism was associated with an increased risk of premature CAD in Chinese subjects, and the association was more significant among male subjects.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-015-0065-7) contains supplementary material, which is available to authorized users.

Association of ATP-Binding Cassette Transporter G1 Polymorphisms with Risk of Ischemic Stroke in the Chinese Han Population

The adenosine triphosphate (ATP)-binding cassette transporter G1 (ABCG1), a member of the superfamily of ATP-binding cassette transporters, is involved in the transport of cholesterol and phospholipids in macrophages. As such, ABCG1 plays a crucial role in the development of atherosclerosis in humans. In this study, we investigate the association between ABCG1 polymorphisms and the risk of developing ischemic stroke in a Chinese Han population. This case-control study included 389 ischemic stroke patients and 380 healthy subjects. ABCG1 rs1378577 and rs57137919 polymorphisms were analyzed by a polymerase chain reaction-ligation detection reaction. We found that the genotypic distribution and allelic frequency of these polymorphisms were similar in patients and controls. In a subgroup with hypertriglyceridemia (144 patients and 115 controls), the frequency of rs1378577 GG genotype and G allele as well as rs57137919 AA genotype was lower in the patient group compared with that in the control group (P=.018, P=.035, and P=.023, respectively). Logistic regression analysis revealed a reduced risk of ischemic stroke in a recessive model for both rs1378577 and rs57137919. Subtype analyses demonstrated that rs1378577TG and GG genotypes and the G allele were associated with reduced risk of atherothrombotic stroke (P=.030, P=.006, and P=.004, respectively), even after adjusting for confounding factors in a dominant model. Data from the present study demonstrate that ABCG1 polymorphisms are associated with reduced risk of developing ischemic stroke in hypertriglyceridemic population and atherothrombotic stroke in this cohort of Chinese Han population.

MiR-146a and miR-196a2 polymorphisms in patients with ischemic stroke in the northern Chinese Han population.

MicroRNAs are endogenous non-coding RNAs about 22 nucleotides in length that can repress the expression of proteins by binding to the 3'-untranslated regions of target messenger RNAs. We hypothesized that polymorphisms in miR-146a and miR-196a2 are associated with risk of ischemic stroke in the northern Chinese Han population. In a case-control study of 368 ischemic stroke patients and 381 control subjects that were frequency matched by age and gender, we genotyped two single nucleotide polymorphisms (rs11614913 in miR-196a2 and rs2910164 in miR-146a) using polymerase chain reaction-ligation detection reaction. The frequencies of the rs2910164 CC genotype and C allele within miR-146a were not significantly different in patients with ischemic stroke compared with those in the healthy control group. In subgroup meta-analysis, rs2910164 in miR-146a and large-artery atherosclerosis, rather than small-vessel disease, showed the significant association under the dominant model (CC vs CG+GG, OR 1.694; 95 % CI 1.199-2.395 p = 0.003). After adjusting for confounding risk factors of ischemic stroke by logistic regression analysis, this significant correlation remained. In addition, the distributions of the miR-196a2 genotypes and alleles were not statistically different between ischemic stroke and healthy groups. We also did not find any significant association from stroke subtypes. The CC genotype and C allele of rs2910164 within miR-146a are associated with an increased incidence of large-artery atherosclerotic stroke in the northern Chinese Han population. This study indicates that miR-146a (rs2910164) might contribute to ischemic stroke susceptibility in the northern Chinese Han population.

The LRP6 rs2302685 polymorphism is associated with increased risk of myocardial infarction.

BackgroundAbnormal lipids is one of the critical risk factors for myocardial infarction (MI), however the role of genetic variants in lipid metabolism-related genes on MI pathogenesis still requires further investigation. We herein genotyped three SNPs (LRP6 rs2302685, LDLRAP1 rs6687605, SOAT1 rs13306731) in lipid metabolism-related genes, aimed to shed light on the influence of these SNPs on individual susceptibility to MI.MethodsGenotyping of the three SNPs (rs2302685, rs6687605 and rs13306731) was performed in 285 MI cases and 650 control subjects using polymerase chain reaction–ligation detection reaction (PCR–LDR) method. The association of these SNPs with MI and lipid profiles was performed with SPSS software.ResultsMultivariate logistic regression analysis showed that C allele (OR = 1.62, P = 0.039) and the combined CT/CC genotype (OR = 1.67, P = 0.035) of LRP6 rs2302685 were associated with increased MI risk, while the other two SNPs had no significant effect. Further stratified analysis uncovered a more evident association with MI risk among younger subjects (≤60 years old). Fascinatingly, CT/CC genotype of rs2302685 conferred increased LDL-C levels compared to TT genotype (3.0 mmol/L vs 2.72 mmol/L) in younger subjects.ConclusionsOur data provides the first evidence that LRP6 rs2302685 polymorphism is associated with an increased risk of MI in Chinese subjects, and the association is more evident among younger individuals, which probably due to the elevated LDL-C levels.

XRCC3 Polymorphisms are Associated with the Risk of Developing Radiation-induced Late Xerostomia in Nasopharyngeal Carcinoma Patients Treated with Intensity Modulation Radiated Therapy

The incidence of radiation-induced late xerostomia varies greatly in nasopharyngeal carcinoma patients treated with radiotherapy. The single-nucleotide polymorphisms in genes involved in DNA repair and fibroblast proliferation may be correlated with such variability. The purpose of this paper was to evaluate the association between the risk of developing radiation-induced late xerostomia and four genetic polymorphisms: TGFβ1 C-509T, TGFβ1 T869C, XRCC3 722C>T and ATM 5557G>A in nasopharyngeal carcinoma patients treated with Intensity Modulation Radiated Therapy. The severity of late xerostomia was assessed using a patient self-reported validated xerostomia questionnaire. Polymerase chain reaction-ligation detection reaction methods were performed to determine individual genetic polymorphism. The development of radiation-induced xerostomia associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for equivalent uniform dose. A total of 43 (41.7%) patients experienced radiation-induced late xerostomia. Univariate Cox proportional hazard analyses showed a higher risk of late xerostomia for patients with XRCC3 722 TT/CT alleles. In multivariate analysis adjusted for clinical and dosimetric factors, XRCC3 722C>T polymorphisms remained a significant factor for higher risk of late xerostomia. To our knowledge, this is the first study that demonstrated an association between genetic polymorphisms and the risk of radiation-induced late xerostomia in nasopharyngeal carcinoma patients treated with Intensity Modulation Radiated Therapy. Our findings suggest that the polymorphisms in XRCC3 are significantly associated with the risk of developing radiation-induced late xerostomia.

Relationship between α-fetoprotein polymorphisms and peripheral α-fetoprotein level in hepatocellular carcinoma patients

Objective To study the relationship betweenα-fetoprotein(AFP)polymorphisms and peripheral AFP level in hepatocellular carcinoma(HCC)patients.Methods Using polymerase chain reaction-ligation detection reaction(PCRLDR)technique,we determined the polymorphisms of AFP of 335 HCC patients;the serum levels of AFP were also determined.SPSS 13.0software was used for statistical analysis.Results The GG genotype frequency of-205CG of AFP gene was significantly different between patients with AFP values≥20and20ng/mL(GG vs CC:χ2=4.389,P=0.036).The frequency of G allele was also found significantly different between patients with AFP values≥400and400ng/mL(G vs C:χ2=4.410,P=0.036).No relationship was found between AFP expression and other polymorphisms,including intron1AT,intron7AG,3′UTR AG and intron2AG,in AFPgene.Conclusion In HCC patients among Chinese Han population,the C allele and CC genotype of-205CG polymorphism site in AFPgene is associated with higher AFP values.

The Pro12Ala Polymorphism of PPAR-γ Gene Is Associated with Sepsis Disease Severity and Outcome in Chinese Han Population.

Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a ligand-binding nuclear receptor, and its activation plays a prominent role in regulating the inflammatory response. Therefore, PPAR-γ has been suggested as a candidate gene for sepsis. In the present study, we investigated the association between the Pro12Ala polymorphism of PPAR-γ and sepsis in a Han Chinese population. A total of 308 patients with sepsis and 345 healthy controls were enrolled in this study. Genotyping was performed using the polymerase chain reaction-ligation detection reaction (PCR-LDR) method. No significant differences were detected in the allele and genotype distributions of the PPAR-γ Pro12Ala SNP between septic patients and controls (P = 0.622 for genotype; P = 0.629 for allele). However, stratification by subtypes (sepsis, septic shock, and severe sepsis) revealed a statistically significant difference in the frequency of the Ala allele and Ala-carrier genotype between the patients with the sepsis subtype and the healthy controls (P = 0.014 for allele and P = 0.012, for genotype). Moreover, significant differences were found in the frequency of the Ala allele and genotype between the sepsis survivors and nonsurvivors (all P = 0.002). In the survivors, the PPAR-γ Pro12Ala genotype was significantly associated with decreased disease severity and recovery time (all P < 0.001). Thus, genetic polymorphism is thought to play a role in the development and outcome of sepsis.

TGF-α gene variations and increased susceptibility of gastric cancer in an eastern Chinese Han population

Transforming growth factor-alpha (TGF-α) correlates with deep invasion, advanced stage and poor prognosis in gastric cancer. Genetic variants in the 3′ untranslated region (UTR) of TGF-α gene may influence the stability and post-transcriptional regulation of mRNA and contribute to gastric cancer predisposition. To test this hypothesis, we genotyped five polymorphisms in 3′UTR (rs3771527, rs503314, rs473698, rs3732253 and rs538118) and one in 3′ near region (rs11466306) of the TGF-α gene by polymerase chain reaction-ligation detection reaction methods (PCR-LDR). We found that GA/AA genotype of rs11466306 in the 3′ near gene could increase the risk of overall gastric cancer (adjusted OR = 1.499, 95%CI: 1.101–2.041), compared to the wild homozygous GG genotype. Meanwhile, the risk effect was more obvious in the intestinal gastric cancer and gastric noncardia cancer (adjusted OR = 1.682, 95%CI: 1.188–2.380; adjusted OR = 1.495, 95%CI: 1.072–2.086, respectively), but not for the diffuse type and gastric cardia cancer (p > 0.05). CT/TT genotype for rs3732253 in the 3′ UTR was associated with increased risk of intestinal gastric cancer (adjusted OR = 1.464, 95%CI: 1.036–2.069), compared to their wild homozygous genotypes. These findings indicate that potentially functional TGF-α gene variant may contribute to the risk of intestinal gastric cancer and/or gastric noncardia cancer and could be used as molecular markers for detecting intestinal gastric cancer and/or gastric noncardia cancer in Chinese Han population.

Association among lifestyle, clinical examination, polymorphisms in CDH1 gene and Traditional Chinese Medicine syndrome differentiation of gastric cancer

ObjectiveTo explore the association among lifestyle, clinical examination, polymorphisms in CDH1 gene and Traditional Chinese Medicine (TCM) syndrome differentiation of gastric cancer (GC). MethodsA hospital-based population of 387 GC patients was investigated in Jiangsu province. Relevant information regarding lifestyle and clinical examination were collected by a standard questionnaire. Four known single nucleotide polymorphisms (SNPs) in CDH1 were investigated by polymerase chain reaction-ligation detection reaction methods. Statistical analysis was conducted by SPSS 16.0 software. ResultsThe results showed that meal duration and the status of glutamic pyruvic transaminase were significantly associated with TCM syndrome differentiation of GC (both P<0.05). None of the four SNPs in the E-cadherin (CDH1) gene achieved significant differences in their distributions among the nine syndrome types of GC (both P>0.05). However, significant differences were observed in rs13689 genotype distributions between several pairs of syndrome types of GC, suggesting that rs13689 is correlated with the syndrome differentiation of GC. ConclusionIntegrated analysis of lifestyle, clinical examination and CDH1 gene polymorphisms can contribute to a better understanding of the GC syndrome types and may improve the efficacy of interventions by stratifying disease according to TCM criteria.