Southern Chinese Han Population Research Articles

Association of the MMP-9 polymorphism and ischemic stroke risk in southern Chinese Han population

BackgroundStroke is a serious cardiovascular disease and is also the leading cause of long-term disability in developing and developed countries. Because matrix metalloproteinase-9 (MMP-9) is associated with the risk of many cardiovascular diseases, we investigated the relationship between single nucleotide polymorphisms (SNPs) in MMP-9 and the risk of Ischemic stroke (IS) in a southern Chinese Han population.MethodsThis study included 250 stroke patients and 250 healthy controls. Genotyping was performed using the Agena MassARRAY system, and chi-squared tests and genetic models were used to evaluate the associations between MMP-9 SNPs and the risk of IS. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusted for age.ResultsPolymorphism rs3787268 was associated with increased the risk of IS. Specifically, the genotype “G/A” significantly correlated with IS risk in the co-dominant model [odds ratio (OR) = 1.62; 95% confidence interval (CI) = 1.10–2.41; p = 0.035)], while genotypes “G/A” and “A/A” may increase the risk of IS based on the dominant model (OR = 1.62; 95% CI = 1.12–2.35; p = 0.0097). This SNP was also significantly associated with IS risk in the log-additive model (OR = 1.33; 95% CI = 1.03–1.70; p = 0.026). Conversely, haplotype “C/G” appears to reduce the risk of IS (OR = 0.71; 95% CI = 0.54–0.95; p = 0.019).ConclusionsOur study showed that the rs3787268 locus in the MMP-9 gene may increase risk of IS in a southern Chinese Han population and thus provide insight into the IS pathogenesis.

HDAC9 Polymorphisms Predict Susceptibility, Severity, and Short-Term Outcome of Large Artery Atherosclerotic Stroke in Chinese Population.

Recently, a genome-wide association study (GWAS) detected two histone deacetylase 9 (HDAC9) polymorphisms (rs2074633 and rs28688791) which may be associated with risk of large artery atherosclerotic (LAA) stroke. This study aimed to investigate whether these two polymorphisms were associated with susceptibility, severity, and short-term outcome of LAA stroke in a southern Chinese Han population. rs2074633 and rs28688791 were genotyped using SNPscan technology in 1011 LAA stroke patients and 1121 healthy controls. Stroke severity on admission and short-term outcome were, respectively, assessed by the National Institute of Health Stroke Scale (NIHSS) score on admission and modified Rankin Scale score at 3months after stroke onset. rs2074633 (P = 0.039) and rs28688791 (P = 0.025) were associated with risk of LAA stroke. In subgroup analysis according to sex and age, this increased risk was only found in males (P = 0.029 for rs2074633; P = 0.013 for rs28688791) and adults aged < 60years (P = 0.009 for rs2074633; P = 0.003 for rs28688791). Moreover, we detected significant interactions between these two polymorphisms and age (Pinteraction = 0.027 for rs2074633; Pinteraction = 0.044 for rs28688791). The CC genotype of rs28688791 (P = 0.037) was also associated with moderate and severe stroke (NIHSS ≥ 6). Additionally, the CC genotype of rs2074633 and rs28688791 (rs2074633, P = 0.019; rs28688791, P = 0.023) showed significant association with unfavorable short-term outcome of LAA stroke. Our results indicated that HDAC9 polymorphisms may be used as biomarkers for susceptibility, severity, and short-term outcome of LAA stroke.

Human Aquaporin 4 Gene Polymorphisms and Haplotypes Are Associated With Serum S100B Level and Negative Symptoms of Schizophrenia in a Southern Chinese Han Population.

Background: Aquaporin 4 (AQP4) polymorphism may influence the required dosage of antipsychotic drugs. However, the roles of AQP4 polymorphisms in the blood—brain barrier (BBB) and different neuroprotective effects need further exploration. This study aims to investigate whether the gene polymorphisms and haplotype of AQP4 are associated with serum S100 calcium-binding protein B (S100B) level and clinical symptoms in patients with schizophrenia (SCZ).Methods: We recruited 190 patients with SCZ. They provided demographic data, completed relevant questionnaires, and submitted samples to test for four AQP4 tag single nucleotide polymorphisms (SNPs) and eight haplotypes. The rating scales of Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance (PSP), the Global Assessment of Functioning (GAF), Clinical Global Impression (CGI) were assessed and serum S100B level were measured repeatedly during antipsychotic treatment at weeks 0 (baseline), 3, 6, and 9. Using generalized estimating equation (GEE) analyses, log-transformed S100B (logS100B) level was tested for associations with haplotype and other dependent variables.Results: Discretization via the median split procedure showed that logS100B level >1.78 or ≤ 1.78 had the best discriminant validity to stratify the patients into two groups. After 9 weeks of treatment, the serum S100B level was decreased. The TAA haplotype of AQP4 SNPs was associated with increased serum S100B level (p = 0.006). The PANSS negative subscale (PANSS-N) (p = 0.001) and Clinical Global Impression–Improvement (CGI-I) (p = 0.003) scores had a positive association with S100B level.Conclusion: Patients with the TAA haplotype of the AQP4 polymorphism are likely to have increased serum S100B level, negative symptoms and poor control of neuroinflammation. A logS100B level >1.78 may be sufficiently specific to predict a higher severity of negative symptoms. Further study including healthy controls and patients with first and recurrent episodes under selective AQP4 modulators will be necessary to explore the profound effects on the treatment of patients with SCZ and may positively influence their overall outcome.

Association Analysis of NLRP3 Inflammation-Related Gene Promotor Methylation as Well as Mediating Effects on T2DM and Vascular Complications in a Southern Han Chinese Population.

Objective: To explore the association between the methylation levels in the promoter regions of the NLRP3, AIM2, and ASC genes and T2DM and its vascular complications in a Southern Han Chinese population and further analyze their interaction and mediating effects with environmental factors in T2DM.Methods: A case-control study was used to determine the association between population characteristics, the methylation level in the promoter region of the NLRP3, AIM2, and ASC genes and T2DM and vascular complications. A mediating effect among genes-environment-T2DM and the interaction of gene-gene or gene-environment factors was explored.Results: In the logistic regression model with adjusted covariants, healthy people with lower total methylation levels in the AIM2 promoter region exhibited a 2.29-fold [OR: 2.29 (1.28~6.66), P = 0.011] increased risk of developing T2DM compared with higher-methylation individuals. T2DM patients without any vascular complications who had lower methylation levels (<methylation median) in NLRP3 CpG2 and AIM2 total methylation had 6.45 (OR: 6.45, 95% CI: 1.05~39.78, P = 0.011) and 9.48 (OR: 9.48, 95% CI: 1.14~79.00, P = 0.038) times higher risks, respectively, of developing diabetic microvascular complications than T2DM patients with higher methylation. Similar associations were also found between the lower total methylation of the NLRP3 and AIM2 promoter regions and macrovascular complication risk (NLRP3 OR: 36.03, 95% CI: 3.11~417.06, P = 0.004; AIM2 OR: 30.90, 95% CI: 2.59~368.49, P = 0.007). Lower NLRP3 promoter total methylation was related to a 17.78-fold increased risk of micro-macrovascular complications (OR: 17.78, 95% CI: 2.04~155.28, P = 0.009). Lower ASC CpG1 or CpG3 methylation levels had significant partial mediating effects on T2DM vascular complications caused by higher age (ASC CpG1 explained approximately 52.8% or 32.9% of the mediating effect of age on macrovascular or macro-microvascular complications; ASC CpG3 explained approximately 38.9% of the mediating effect of age on macrovascular complications). No gene-gene or gene-environment interaction was identified in T2DM.Conclusion: Lower levels of AIM2 promoter total methylation might increase the risk of T2DM. NLRP3, AIM2, and ASC promoter total methylation or some CpG methylation loss might increase the risk of T2DM vascular complications, which merits further study to support the robustness of these findings.

HCN4 Gene Variations in Sudden Unexplained Nocturnal Death Syndrome in the Southern Han Chinese Population.

Sudden unexplained nocturnal death syndrome (SUNDS) is widely considered to be related to hereditary fatal arrhythmias. Hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) channels are widely distributed in sinus myocytes and play a profound role in generating pacemaker electro-activity in cardiomyocytes. In the present study, the potential correlation between HCN4 gene variations and the occurrence of SUNDS was investigated. Genomic DNA was extracted from blood samples of both 119 unrelated SUNDS patients and 184 healthy individuals and screened for candidate HCN4 gene variants. One missense heterozygous variant c.1578C>T (Ala195Val) and four synonymous heterozygous variants c.1552C>T, c.2833C>T, c.3823C>T, and c.4189C>A were discovered in the SUNDS cases. The missense variant c.1578C>T (Ala195Val) was absent in 163 recruited controls and 105 persons of the Southern Han Chinese population, had in-silico prediction indications as damaging, and was reported prevalent in sudden infant death, and is thus likely to be involved in SUNDS.

Serum PCSK9 levels, but not PCSK9 polymorphisms, are associated with CAD risk and lipid profiles in southern Chinese Han population

BackgroundGenetic and environment factors affect the occurrence and development of coronary artery disease (CAD). Proprotein convertase subtilisin/kexin type 9 (PCSK9), has been investigated extensively in the field of lipid metabolism and CAD. We performed this case-control study to investigate the relationship between serum PCSK9 levels and PCSK9 polymorphisms and lipid levels and CAD risk in a southern Chinese population.MethodsA hospital-based case-control study with 1, 096 subjects, including 626 CAD patients and 470 controls, were conducted. Genotyping of PCSK9 polymorphisms was performed using polymerase chain reaction-ligase detection reaction (PCR-LDR) method.ResultsThe frequencies of the AA, AG and GG genotypes of PCSK9 E670G polymorphism were 90.58, 9.27, and 0.16% in the CAD patients, compared with 88.72, 10.85 and 0.43% in the controls, respectively. No R46L variant was detected in this population. There were no significant differences in genotype and allele frequencies of PCSK9E670G polymorphism between the CAD group and the controls. Serum lipid levels were not significantly different in carriers with the G allele and those with the AA genotype. The median (QR) of PCSK9 concentration was 1205.00 ng/l (577.28–1694.13 ng/l) in cases and 565.87 ng/l (357.17–967.50 ng/l) in controls, respectively. Compared with controls, CAD patients had significantly higher PCSK9 levels (z = 4.559, P < 0.001). After adjusting for age, gender, essential hypertension, diabetic mellitus, smoking and lipid profiles, PCSK9 levels remain significantly associated with increased CAD susceptibility (OR = 1.002, 95% CI = 1.001–1.002, P < 0.001). The correlation analyses showed that serum PCSK9 levels were positively associated with triglyceride (TG), Apo B and atherogenic index of plasma (AIP) levels in controls. No significant association between the PCSK9 E670G polymorphism and serum PCSK9 levels was observed in the CAD group and the controls.ConclusionsThe present study shows that serum PCSK9 levels, but not PCSK9 polymorphisms, are associated with CAD risk in Southern Chinese Han population, and that serum PCSK9 levels are positively associated with AIP.

Accuracy of the Demirjian and Willems methods of dental age estimation for children from central southern China.

The aim of this study was to compare the accuracy of the Demirjian method and the Demirjian method as revised by Willems for age estimation based on orthopantomograms from central southern Chinese Han population aged 8-16years. Discrepancies between chronological and estimated ages were statistically evaluated by analyzing 1249 orthopantomograms from 603 girls and 646 boys. Using the Demirjian method, the mean age estimates underestimated chronological age by 0.03years (p = 0.48) for girls and overestimated it by 0.03years (p = 0.59) for boys; these differences with respect to chronological age were not statistically significant. In contrast, the Willems method underestimated chronological age by 0.54years (p < 0.01) for girls and 0.44years (p < 0.01) for boys; these differences with respect to chronological age were statistically significant. Compared to the Demirjian method, the overall mean absolute error generated using the Willems method was slightly higher (0.85 and 0.86years, respectively). Since the Demirjian method was more accurate, we highly recommend that it should be applied when estimating dental age in the Chinese Han population. Further modifications of these two methods for populations from other regions and additional studies of other age groups are warranted.

Association between the MVK rs2287218 SNP and the risk of coronary heart disease and ischemic stroke: A case-control study.

The association between the mevalonate kinase gene (MVK) single nucleotide polymorphism (SNP) and serum lipid levels has been detected in several previous genome-wide association studies, but the results are inconsistent. In addition, it is still unclear whether the loci indentified exert the similar effect on the susceptibility of coronary heart disease (CHD) or ischemic stroke (IS). Therefore, the present study was undertaken to detect the association between the MVK rs2287218 SNP and serum lipid levels, the susceptibility of CHD and IS in a Southern Chinese Han population. The genotypes of the SNP in 1764 unrelated subjects (CHD, 583; IS, 555; and healthy controls, 626) were determined by the Snapshot technology. The genotypic and allelic frequencies were different between CHD and control subjects (P ≤ 0.013 for each), or between IS and control groups (P < 0.01 for each). The T allele carriers had an increased risk of CHD and IS (CHD: OR = 1.674, 95%CI = 1.25-2.25, P = 0.001 for CT/TT vs. CC genotypes; OR = 1.595, 95%CI = 1.23-2.07, P < 0.001 for T vs. C alleles; IS: OR = 1.890, 95%CI = 1.36-2.47, P = 0.001 for CT/TT vs. CC genotypes; OR = 1.829, 95%CI = 1.38-2.42, P < 0.001 for T vs. C alleles). The T allele carriers in healthy controls had lower serum high-density lipoprotein cholesterol (HDL-C) levels than the T allele non-carriers (P = 0.013). These findings suggest that the MVK rs2287218 SNP is likely to increase the risk of CHD and IS by decreasing serum HDL-C levels in our study populations.

The ANGPTL4 Variants, Their Haplotypes and G×E Interactions on Serum Lipid Levels, Coronary Artery Disease, Ischemic Stroke and Response to Atorvastatin Therapy

Background: This study aimed to assess the association of the angiopoietin-like protein 4 gene (ANGPTL4) variants and serum lipid levels, the risk of coronary artery disease (CAD) and ischemic stroke (IS), and response to atorvastatin therapy in a Southern Chinese Han population. Methods: Genotypes of the ANGPTL4 rs4076317, rs7255436, rs1044250 and rs2967605 in 1,654 unrelated subjects (CAD, 568; IS, 537; and controls, 549) were determined by the Snapshot technology. A total of 724 hyperlipidemic patients were treated with atorvastatin calcium tablet 20 mg/day for 8 weeks. Results: The rs2967605 CT/TT genotypes were associated with a decreased risk of CAD (adjusted OR=0.68, 95% CI=0.47-0.99, P=0.043 for CT/TT vs. CC) and IS (adjusted OR=0.55, 95% CI=0.38-0.80, P=0.020 for CT/TT vs. CC). Significant interactions were observed in gender, body mass index, alcohol consumption and diabetes. There were no significant effects of the four SNPs on angiographic severity of CAD. The subjects with the rs4076317 CG/CC genotypes in controls had higher total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels than the subjects with the GG genotype (P < 0.001). Functional predictions of the rs2967605 and rs4076317 were carried out using bioinformatics tools F-SNP. The results showed changes in the level of transcriptional regulation. The subjects with rs4076317CG/GG genotypes had lower TC and LDL-C levels than the subjects with CC genotype after atorvastatin treatment. Conclusions: The observed associations suggest that the ANGPTL4 variants have a potential role on serum lipid levels and atherosclerosis-related diseases in the Han population, especially ANGPTL4 rs4076317. Funding Statement: This study was supported by the Science Foundation of Guangxi Returned Oversea Scholars (No. 0991004) and the National Natural Science Foundation of China (No. 81460169). Declaration of Interests: All authors declare that they have no competing interest. Ethics Approval Statement: The study protocol was approved by the Ethics Committee of our First Affiliated Hospital (No. Lunshen 2009-Guike-018). Informed consent was obtained from all subjects.

Associations of TF Gene Polymorphisms with the Risk of Ischemic Stroke.

Ischemic stroke (IS) is the main cause of mortality and disability in China; thus, this study aimed to examine the association between six variants and their haplotypes within the transferrin (TF) gene and the risk of IS in the Southern Chinese Han population. Genotyping was performed using the Sequenom MassARRAY platform for 249 IS patients and 249 age- and sex-matched controls. The association between polymorphisms and IS risk was tested by Chi squared test and haplotype and stratification analysis. Odds ratios (ORs) and confidence intervals (CIs) were estimated by unconditional logistic regression analysis. The results of genetic model analyses indicated that the two SNPs (rs1880669 and rs2692695) were associated with decreased IS risk under the co-dominant, dominant, and additive models. Additionally, rs4525863 was also associated with decreased IS risk both under the dominant and additive models in males. Moreover, the CG haplotype of TF (rs1880669 and rs2692695) was significantly associated with a decreased risk of IS in the total population and males. Our findings suggested that polymorphisms (rs4525863, rs1880669, and rs2692695) of the TF gene might be a protective factor for IS in Southern Chinese Han population. Further large prospective studies are required to confirm these findings.

The intragenic epistatic association of ADD3 with biliary atresia in Southern Han Chinese population.

Biliary atresia (BA) is a multifactorial pathogenic disease with possible genetic components. As a member of membrane skeletal proteins in the liver and bile ducts, a haplotype composed by five single nucleotide polymorphisms (SNPs) on adducin 3 (ADD3) has been identified as associated with BA. However, limited study was designed to further elaborate the mutual relationship amongst those replicated SNPs to disease. We selected three susceptibility SNPs in ADD3 and conducted a replication study using 510 BA cases and 1473 controls to evaluate the individual function of the SNPs and further stratified the potential roles with disease and its subclinical features. Two SNPs in ADD3 were replicated as associated with BA (1.60E-04 ≤ P≤1.70E-04, 1.33 ≤ odds ratio (OR) ≤ 1.58 for rs17095355, 2.10E-04 ≤ P≤5.30E-04, 1.26 ≤ OR ≤ 1.57 for rs2501577). Though we failed to replicate the individual association of rs10509906 to disease, the intragenic epistatic effect between rs10509906 and rs2501577 was suggested as exhibiting susceptibility to BA, further cross-validated by multifactor dimensionality reduction (MDR) (P=0.068, OR = 1.37), which may explain extra hidden heritability of ADD3 to BA. Furthermore, through subclinical stratification, we also observed the association of risk to disease mainly came from the female patients.

Evaluation of genetic parameters of 23 autosomal STR loci in a Southern Chinese Han population

Aim: To evaluate the 23 autosomal short tandem repeat (STR) loci included in GoldenEye™ 25 A kit using forensic human identification and paternity testing.Subjects and methods: In total, 3751 unrelated individuals from the Southern Chinese Han population were genotyped with the 5-dye GoldenEye™ 25 A multiplex amplification system. PCR products were separated using arrayed capillary electrophoresis. Allele frequencies and forensic parameters for the 23 autosomal STR loci were statistically analysed.Results: A total of 344 alleles were observed, with corresponding allelic frequencies ranging from 0.0001–0.5519 for the 23 STR loci. No significant deviation from the Hardy-Weinberg equilibrium and linkage disequilibrium was observed. The combined power of discrimination (CPD) was 1–1.6290 × 10−28 and the combined power of exclusion (CPE) was 0.999 999 999 89 and 0.999 999 286 93 for trio and duo cases, respectively. From 3865 meioses, 87 mutation events were discovered. The mutation rate varied from 0–0.00285 for each locus. One-step mutation accounted for 94.25% of total mutations. The ratio of paternal vs maternal mutation was 3.76:1.13 kinds of n/(n + 1) heterozygote genotypes were observed.Conclusions: The results show that 23 STR loci of GoldenEye™ 25 A kit are highly polymorphic in the Southern Chinese Han population, indicating the kit is suitable for forensic application.

Association between the PPP1R3B polymorphisms and serum lipid traits, the risk of coronary artery disease and ischemic stroke in a southern Chinese Han population

BackgroundLittle is known about the association of the protein phosphatase 1 regulatory subunit 3B gene (PPP1R3B) single nucleotide polymorphisms (SNPs) and serum lipid levels, the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Chinese populations. This study detected such association in a Southern Chinese Han population.MethodsGenotypes of 4 novel PPP1R3B SNPs (rs12785, rs330910, rs330915 and rs9949) in 1704 Han Chinese (CAD, 556; IS, 531 and control, 617) were determined by the Snapshot technology.ResultsThe rs12785A and rs9949A allele frequency was higher in both CAD/IS patients than in controls. The rs330910T and rs330915T allele frequency was also higher in CAD patients than in controls. The rs330910T allele carriers in controls had lower serum low-density lipoprotein cholesterol (LDL-C) levels than the rs330910T allele non-carriers (P < 0.0014). The rs12785A, rs9949A and rs330910T allele carriers were associated with an increased risk of CAD (P = 0.008–0.004). There was strong linkage disequilibrium among the 4 SNPs in the controls and CAD/IS patients. The T-A-A-G haplotype was associated with a decreased risk of CAD and IS, whereas the A-A-T-A haplotype was associated with an increased risk for IS. Haplotype-environment interactions on the risk of CAD and IS were also observed.ConclusionsSeveral PPP1R3B polymorphisms were associated with serum LDL-C levels, the risk of CAD and IS in the Southern Chinese Han population. But these findings still need to be confirmed in the other populations with larger sample sizes.

Association between PLA2G12A polymorphism and patients with schizophrenia in a southern Chinese Han population.

Elevated phospholipase A2 (PLA2) activity is reported to be involved in the development of schizophrenia. Further study revealed an association between PLA2 groups XIIA (PLA2G12A) polymorphism and patients with schizophrenia in a northeast Chinese Han population. This study will further examine whether PLA2G12A rs3087494 polymorphism is associated with patients with schizophrenia in a southern Chinese Han population. This polymorphism was genotyped in 438 patients with schizophrenia (diagnosed according to Diagnostic and Statistical Manual of Mental Disorders-IV) and 876 healthy controls using a case-control design. Demographic and clinical data were collected in all subjects. The allele and genotype frequencies of PLA2G12A rs3087494 polymorphism significantly differed between groups (both, p<.001). These differences still were significant by adjusting for sex and age. However, there was no difference in age at onset among 3 genotype groups in patients with schizophrenia by adjusting for the variables (F=0.22, p=.80). Stepwise multivariate regression analysis showed that this polymorphism was not associated with age at onset in patients with schizophrenia (β=.008, t=.07, p=.94). Our results indicated that even though PLA2G12A rs3087494 polymorphism did not influence age at onset in patients with schizophrenia, it may play an important role in the susceptibility to schizophrenia in a southern Chinese Han population.

DOCK7-ANGPTL3 SNPs and their haplotypes with serum lipid levels and the risk of coronary artery disease and ischemic stroke

BackgroundLittle is known about the association of the dedicator of cytokinesis 7 (DOCK7 rs1748195) and angiopoietin like 3 (ANGPTL3 rs12563308) single nucleotide polymorphisms (SNPs) and their haplotypes with serum lipid levels and the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Chinese populations. This study aimed to detect such association in a Southern Chinese Han population.MethodsThis study included 1728 subjects (CAD, 568; IS, 539; and controls, 621). Genotypes of the two SNPs were determined by the Snapshot technology.ResultsThe genotypic and allelic frequencies of the rs1748195 SNP were different between CAD patients and controls (P < 0.05 for each), the rs1748195G allele frequency was higher in CAD patients than in controls (27.6% vs. 23.6%, P = 0.024). The genotypic frequencies of the rs12563308 SNP were also different between CAD patients and controls (P = 0.021). The rs1748195 SNP was associated with an increased risk of CAD after controlling for potential confounders and Bonferroni correction (P < 0.025 considered statistically significant; Recessive: OR = 1.79, 95% CI = 1.04-3.06, P = 0.017; Log-additive: OR = 1.27, 95% CI = 1.02-1.57, P = 0.014), whereas the rs12563308 SNP was associated with a decreased risk of CAD (Dominant: OR = 0.69, 95% CI = 0.45-0.94, P = 0.011; Log-additive: OR = 0.73, 95% CI = 0.49-0.89, P = 0.009). The rs1748195 SNP was also associated with an increased risk of severity to coronary artery atherosclerosis (Dominant: OR = 1.45, 95% CI = 1.07-2.11, P = 0.017; Log-additive: OR = 1.35, 95% CI = 1.09-1.82, P = 0.013). The interactions of SNP-environment on serum lipid levels and the risk of severity to coronary artery atherosclerosis, CAD and IS were noted. The rs1748195G-rs12563308T haplotype was associated with an increased angiographic severity to coronary artery atherosclerosis (OR = 1.46, 95% CI = 1.05-2.03), and the risk of CAD (OR = 1.37, 95% CI = 1.08-1.74). The interactions of haplotype-hypertension on the risk of CAD and haplotype-drinking on the risk of CAD/IS were observed.ConclusionsThese results suggest that the DOCK-ANGPTL3 SNPs and their haplotypes were associated with the angiographic severity to coronary artery atherosclerosis and the risk of CAD and IS in the Southern Chinese Han population.

Association between the TIMD4-HAVCR1 variants and serum lipid levels, coronary heart disease and ischemic stroke risk and atorvastatin lipid-lowering efficacy.

Little is known about the association of the TIMD4 (T-cell immunoglobulin and mucin domain 4 gene)-HAVCR1 (hepatitis A virus cellular receptor 1) variants and lipid metabolism, the risk of coronary heart disease (CHD) and ischemic stroke (IS). The present study aimed to determine the TIMD4-HAVCR1 variants, their haplotypes and gene–environment interactions on serum lipid levels, the risk of CHD and IS, and the lipid-lowering efficacy of atorvastatin in a southern Chinese Han population. Genotypes of three variants in 622 controls, 579 CHD, and 546 IS patients were determined by the Snapshot technology. Atorvastatin calcium tablet (20 mg/day) was given in 724 hyperlipidemic patients for 8 weeks after genotyping. The rs12522248 genotypic and allelic frequencies were different between controls and patients, and were associated with the risk of CHD and IS. The rs1501908G-rs12522248T-rs2036402T haplotype was associated with an increased risk of CHD; the G-C-T haplotype was associated with lower risk of CHD; and the C-C-C haplotype was associated with an increased risk of IS. Variants and their haplotypes in controls were associated with triglyceride (rs1501908), low-density lipoprotein cholesterol (LDL-C, rs1501908, G-T-T), high-density lipoprotein cholesterol (HDL-C, rs12522248, C-C-C) and the ratio of total cholesterol (TC) to HDL-C (C-C-C). Interactions of rs1501908- and rs2036402-alcohol (HDL-C); rs1501908- and rs12522248-high body mass index (hBMI, ≥24 kg/m2; TC); and TIMD4-HAVCR1 variants-atorvastatin on several lipid parameters were detected. Interactions of rs12522248TC/CC-hBMI, G-T-T-, and C-C-C-smoking on the risk of CHD; and C-C-C-smoking, C-C-C-, and G-C-T-hBMI on the risk of IS were also observed. These findings suggest that the TIMD4-HAVCR1 variants may be the genetic risk factors for CHD and IS.

Lack of Association between DMT1 Polymorphism and Iron Overload in Chinese Patients with Parkinson’s Disease

Objective: Iron overload in the substantia nigra (SN) has been suggested playing a role in causing Parkinson’s disease (PD), but the underlying mechanism leading to iron accumulation is not clear. Divalent metal transporter 1 (DMT1), an endogenous transporter for ferrous iron, has been suggested being involved in iron metabolism in both animal model and PD patients. However, previous studies failed to reveal DMT1 as strong risk factor for PD patients. One reason might be that abnormal iron accumulation is not a universal pathogenesis for PD patients. This study aims to explore whether DMT1 is a risk factor for PD patients with or without iron overload. Methods: Transcranial sonography (TCS) was used to classify PD patients into two subgroups, PD with SN hyperechogenicity (SN+) and PD without SN hyperechogenicity (SN-), to study the possible association between DMT1 gene variants and iron overload in PD patients. One mutation (1303C/A) and two single nucleotide polymorphisms (SNPs) (1254T/C and IVS4 + 44C/A) of DMT1 gene were tested in 67 PD SN+ patients and 53 PD SN- patients of Southern Han Chinese population by method of polymerase chain reactionrestriction fragment length polymorphism (PCR–RFLP). Results: Distribution of Genotypes and allele frequencies of all these three sites didn’t show significant difference between PD SN+ and PD SN- patients. Haplotype analysis of 1254T/C and IVS4 + 44C/A didn’t reveal potential risk factor for iron overload. Conclusion: Our results suggested that DMT1 gene variants (1303C/A, 1254T/C and IVS4 + 44C/A) are not correlated with iron accumulation in PD patients.

Association of polymorphism in the VEGFA gene 3'-UTR +936T/C with susceptibility to biliary atresia in a Southern Chinese Han population.

Biliary atresia (BA) is a neonatal disease characterized by chronic inflammation of the bile ducts and progressive aggravation of jaundice, but with a poor prognosis and high mortality. The etiology of BA is still uncertain which may be related to gene defect, virus infection, immune disorder, gene polymorphism. As a proinflammatory cytokine, VEGFA gene polymorphism (rs3025039) has been shown to be related to the pathogenesis of BA in Taiwanese population. We investigated the association between VEGFA gene polymorphism (rs3025039) and BA susceptibility using the largest case-control cohort, totaling with 506 BA patients and 1473 healthy controls in a Southern Chinese Han population. VEGFA gene polymorphism (rs3025039) was genotyped using the MassARRAY iPLEX Gold system (Sequenom). Odds ratios (OR) and 95% confidence intervals (CIs) were used to access the association between the VEGFA gene polymorphism (rs3025039) and BA risk. No significant association was found between the VEGFA gene polymorphism (rs3025039) and BA risk in the overall analysis. These results suggest that VEGFA gene polymorphism (rs3025039) may not be associated with the risk of BA in the Southern Chinese Han population.

Association of SNPs in the TIMP-2 gene and large artery atherosclerotic stroke in southern Chinese Han population.

Tissue inhibitor of matrix metalloproteinase 2 (TIMP-2) regulates the extracellular matrix degradation, which involved in vascular remodeling and dysfunction, destabilization of atherosclerotic plaque and many other pathological processes. The rupture of atherosclerotic plaque is the trigger of Large artery atherosclerotic (LAA) stroke. We speculate that the Single nucleotide polymorphisms (SNPs) in TIMP-2 may have an association with LAA stroke. To prove this hypothesis, we conducted this case-control study. 250 LAA stroke patients and 250 healthy controls were collected for the analysis of TIMP-2 polymorphisms. Among six SNPs, we detected no deviation from Hardy-Weinberg equilibrium in control group. There was a significant difference in rs4789936 T allele frequency between patient and control groups (OR = 0.68, 95% CI = 0.51–0.91, P = 0.009), which means lower risk of LAA stroke. We observed the rs4789936 had a decreased risk of LAA stroke according to the codominant (OR = 0.64, 95% CI = 0.44–0.92, P = 0.026), dominant (OR = 0.62, 95% CI = 0.43-0.88, P = 0.008), overdominant (OR = 0.68, 95% CI = 0.48–0.98, P = 0.039), log-additive (OR = 0.68, 95% CI = 0.51–0.91, P = 0.009) models analyses. However, these findings could only validate under dominant model (OR = 0.65, 95% CI = 0.42–1.00, P = 0.049) after adjustment of gender and age. The results indicate a potential association between TIMP-2 variants and LAA stroke risk in southern Chinese Han population.

P2X7 receptor in spinal tuberculosis: Gene polymorphisms and protein levels in Chinese Han population

Spinal tuberculosis (TB) accounts for 1%–5% of all TB infections. Host genetic variation influences susceptibility to Mycobacterium tuberculosis (MTB). P2X7 receptor (P2X7R) expressed on cells has been identified as a regulatory molecule in cell death/apoptosis, killing of intercellular pathogens, and bone turnover. This study investigated the P2X7 gene polymorphisms and protein levels in spinal TB. P2X7 gene -762C>T and 489C>T polymorphisms were genotyped. The expression of P2X7R in bone or intervertebral disc (ID) tissues was analyzed by Western blot assay. The -762C>T and 489C>T polymorphisms were associated with susceptibility to spinal TB. Having the -762CC genotype and -762C allele increased the risk of developing spinal TB (CC vs. TT: P=0.031, OR [95%CI]=1.865 [1.053–3.304]; C vs. T: P=0.028, OR [95%CI]=1.355 [1.034–1.775]). The presence of the 489T allele was associated with an increased risk of developing spinal TB (TT vs. CC: P=0.004, OR [95%CI]=2.248 [1.283–3.939]; CT vs. CC: P=0.044, OR [95%CI]=1.755 [1.011–3.047]; T vs. C: P=0.004, OR [95%CI]=1.482 [1.134–1.936]; TT+CT vs. CC: P=0.010, OR [95%CI]=1.967 [1.171–3.304]; TT vs. CT+CC: P=0.037, OR [95%CI]=1.489 [1.023–2.167]). The expression of P2X7R in TB-induced bone lesions increased significantly among spinal TB patients (t=0.011). Carrying the P2X7 -762CC genotype and 489T allele is associated with an increased risk of developing spinal TB in a Southern Chinese Han population.