Northern Chinese Han Population Research Articles

IL1F7 Gene Polymorphism Is not Associated with Rheumatoid Arthritis Susceptibility in the Northern Chinese Han Population: A Case-Control Study.

Background:Interleukin (IL)-37, also called IL1F7, is a natural inhibitor of inflammatory and immune responses. It is involved in the pathogenesis of rheumatoid arthritis (RA). This study aimed to investigate the role of IL1F7 gene polymorphism in RA susceptibility in a large cohort of patients.Methods:Five selected single-nucleotide polymorphisms in IL1F7 genes (rs2723186, rs3811046, rs4241122, rs4364030, and rs4392270) were genotyped by TaqMan Allelic Discrimination in Northern Chinese Han population. The allele and the genotype were compared between patients with RA and healthy controls. Association analyses were performed on the entire data set and on different RA subsets based on the status of the anti-cyclic citrullinated peptide antibody and the rheumatoid factor by logistic regression, adjusting for age and gender.Results:Trend associations were detected between rs2723186, rs4241122, rs4392270, and RA in Stage I (160 patients with RA; 252 healthy controls). Further validation in Stage II comprised 730 unrelated patients with RA (mean age: 54.9 ± 12.6 years; 81.6% females) and 778 unrelated healthy individuals (mean age: 53.5 ± 15.7 years; 79.5% females). No significant differences in the distributions of alleles and genotypes were observed between the case and control groups in both the entire set and the different RA subsets. Disease activity and age of RA onset were also not associated with genotype distributions.Conclusion:IL1F7 gene polymorphism does not significantly influence RA susceptibility in the Northern Chinese Han population.

Associations between thromboxane A synthase 1 gene polymorphisms and the risk of ischemic stroke in a Chinese Han population.

Thromboxane A synthase 1 (TBXAS1) catalyses the synthesis of thromboxane A2 (TXA2), which plays an important role in the pathogenesis of ischemic stroke. Thus, the TBXAS1 gene was investigated as a candidate gene involved in the formation of atherosclerosis. This case-control study collected peripheral blood specimens and clinical data of 370 ischemic stroke patients and 340 healthy controls in the Northern Chinese Han population from October 2010 to May 2011. Two TBXAS1 single-nucleotide polymorphisms, rs2267682 and rs10487667, were analyzed using a SNaPshot Multiplex sequencing assay to explore the relationships between the single-nucleotide polymorphisms in TBXAS1 and ischemic stroke. The TT genotype frequency and T allele frequency of rs2267682 in the patients with ischemic stroke were significantly higher than those in the controls (P < 0.01 and P = 0.02). Furthermore, compared with the GG + GT genotype, the TT rs2267682 genotype was associated with increased risk of ischemic stroke (odds ratio (OR) = 1.80, 95% confidence interval (CI): 1.16-2.79, P < 0.01). Multivariate logistic analysis with adjustments for confounding factors revealed that rs2267682 was still associated with ischemic stroke (OR = 1.94, 95% CI : 1.13-3.33, P = 0.02). The frequency of the T-G haplotype in the patients was significantly higher than that in the controls according haplotype analysis (OR = 1.49, 95% CI: 1.10-2.00, P < 0.01). These data reveal that the rs2267682 TBXAS1 polymorphism is associated with ischemic stroke. The TT genotype of TBXAS1 and T allele of rs2267682 increase susceptibility to ischemic stroke in this Northern Chinese Han population. The protocol has been registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-COC-17013559).

Association of HLA class I and class II alleles with bullous pemphigoid in Chinese Hans

BackgroundBullous pemphigoid (BP) is one of the most common autoimmune skin diseases. Associations of genes, especially human leukocyte antigen (HLA)-DQ alleles, with BP indicate that genetic predisposition contributes to the disease. ObjectivesTo evaluate the association of HLA class I and HLA class II alleles with susceptibility to BP in the northern Chinese Han population. MethodsWe performed genotype for HLA-A, -B, -C, -G, -DPA1, -DPB1, -DQA1, -DQB1 and -DRB1 loci in 105 patients with BP by Sanger sequence-based typing (SBT) method. These data were compared with a local control cohort of 420 age- and sex-matched cases. ResultsAmong the HLA alleles described herein, the susceptibility alleles associated with a high prevalence of BP were A*11:01 (OR = 1.9 Pc = 0.017); B*37:01 (OR = 8, Pc = 1.811 × 10−6); G*01:01 (OR = 3.61, Pc = 2.839 × 10−15) and G*01:06 (OR = 2.22, Pc = 0.025); DQA1*01:05 (OR = 4.87, Pc = 5.822 × 10−5), DQA1*05:05 (OR = 2.64, Pc = 9.114 × 10−4), and DQA1*05:08 (OR = 10.2, Pc = 0.016); DQB1*03:01 (OR = 1.69, Pc = 0.048) and DQB1*05:01 (OR = 3.42, Pc = 7.28 × 10−6); and DRB1*10:01 (OR = 6.85, Pc = 2.63 × 10−6). To the contrary, HLA-DQA1*01:02 (OR = 0.46, Pc = 8.603 × 10−4) and DQA1*01:03 (OR = 0.38, Pc = 0.048); DQB1*02:02 (OR = 0.28, Pc = 0.016); and DRB1*07:01 (OR = 0.26, Pc = 0.004) had significant associations with protection against BP. In addition, the frequency of haplotype HLA-DRB1*13-DQA1*05-DQB1*03 (OR = 12.32, Pc = 0.026) in BP patients was significantly higher than those in controls. ConclusionOur data demonstrated that the alleles and haplotypes found in this study may be important differential genetic markers for susceptibility to or protection against BP in individuals of northern Chinese Han population.

Identification of susceptibility loci for thoracic ossification of the posterior longitudinal ligament by whole-genome sequencing.

Ossification of the posterior longitudinal ligament (OPLL) is a myelopathy commonly observed in the cervical spine. By contrast, thoracic OPLL (T‑OPLL) is rare but more severe. Previous studies have identified several polymorphisms in osteogenic genes that are associated with the occurrence and development of cervical OPLL. However, few genetic studies have evaluated T‑OPLL. The present study aimed to identify the genetic factors for OPLL by performing whole‑genome sequencing (WGS) in 30 unrelated northern Chinese Han patients with T‑OPLL. Using bioinformatics analyses and damaging‑variant prediction algorithms, two deleterious variants [c.1534G>A(p.Gly512Ser)/collagen, type VI,α1 (COL6A1)] and [c.2275C>A(p.Leu759Ile)/inteleukin-17 receptorC (IL17RC)] were identified in seven unrelated patients. These two mutations resulted in markedly increased gene expression levels in peripheral blood samples. To the best of our knowledge, this is the first report to describe the use of WGS analysis of T‑OPLL in the northern Chinese Han population. The results revealed two novel potentially pathogenic mutations in patients with T‑OPLL.

Influence of LGALS3 gene polymorphisms on susceptibility and prognosis of dilated cardiomyopathy in a Northern Han Chinese population

BackgroundGalectin-3 plays an important role in modulating cardiac inflammation and fibrosis. It also takes part in the pathways underlying cardiac remodeling. Therefore, LGALS3 gene, encoding galectin-3 protein, is a promising candidate for the genetic study of dilated cardiomyopathy (DCM). To date, there has been no research evaluating the association between LGALS3 gene polymorphisms and the susceptibility and prognosis of DCM. Methods and ResultsGenotyping of 4 single nucleotide polymorphisms (SNPs) in the LGALS3 gene, which were reported to be functional in the literature, was performed in 279 unrelated clinically diagnosed DCM patients and 363 apparently healthy controls from Northern Han Chinese population using iPLEX SNP Genotyping analysis on a Sequenom MassARRAY System. The frequency of G allelic polymorphism of rs1009977 and the C allelic polymorphism of rs4652 were lower in DCM patients (OR=0.77, 95% CI [0.60–0.99], P=0.045; OR=0.79, 95% CI [0.63–0.99], P=0.042, respectively). The minor variants of rs1009977 and rs4652 were associated with low susceptibility of DCM under additive genetic models (P=0.045 and P=0.040, respectively). The AA genotype of both rs2274273 and rs4644 was associated with lower left ventricular ejection fraction (recessive model, P=0.018 for both; additive model, P=0.039 for both). The G variant of rs1009977 was related with lower serum galectin-3 level in DCM patients under three genetic models (additive model, P=0.020, dominant model, P=0.020, recessive model, P=0.037). The A variant of both rs2274273 and rs4644 was associated with lower level of galectin-3 in DCM patients under additive model (P=0.032 for both) and dominant model (P=0.012 for both). None of the 4 SNPs was associated with the cardiovascular or all-cause death rate of DCM. In Conclusion, LGALS3 gene polymorphisms might be associated with the susceptibility of DCM in a Northern Han Chinese population.

Single nucleotide polymorphisms in the ETS1 gene are associated with idiopathic inflammatory myopathies in a northern Chinese Han population

Single-nucleotide polymorphisms (SNPs) in the ETS1 gene are associated with several auto-inflammatory diseases. In this study, we determined whether ETS1 gene polymorphisms confer susceptibility to idiopathic inflammatory myopathies (IIMs) in a northern Chinese Han population. DNA samples were collected from 1017 IIM patients: 363 PM cases and 654 DM cases. The results were compared with those of 1280 healthy controls. Five SNPs in the ETS1 region (rs7117932, rs6590330, rs4937362, rs10893845 and rs1128334) were assessed and genotyped using the Sequenom platform. Our data indicated that the rs7117932 alleles and genotypes are associated with DM and IIMs (Pc = 6.0 × 10−3 and Pc = 0.029; Pc = 0.013 and Pc = 0.019, respectively). We found a significantly greater percentage of DM and IIM patients with an A allele of rs6590330 than that in the control population (Pc = 0.033 and Pc = 0.013). Additionally, the rs6590330 genotype was associated with IIMs (Pc = 0.020). The percentages of rs7117932 and rs6590330 SNPs were significantly greater in DM and IIM patients with interstitial lung disease (ILD) (all Pc < 0.05). This is the first study to reveal that ETS1 polymorphisms are associated with IIMs alone and IIMs with ILD in a northern Chinese Han population.

Association of HLA-DRB1 polymorphism with Alzheimer's disease: a replication and meta-analysis.

Genome-wide association studies (GWAS) have identified one single-nucleotide polymorphism (SNP) rs9271192 within HLA-DRB1 as a risk factor for Alzheimer's disease (AD) in Caucasians. The effect of rs9271192 on AD needed to be verified in other ethnic cohorts. In order to evaluate the association between HLA-DRB1 rs9271192 polymorphism and late-onset AD (LOAD) in the Northern Han Chinese population, we recruited 982 LOAD patients and 1344 sex- and age-matched healthy controls. The results showed that HLA-DRB1 rs9271192 was associated with LOAD (genotype P = 0.015, allele P = 0.04). The results of logistic regression revealed the C allele homozygosity strongly increased the risk of LOAD under a recessive model in the total sample (P = 0.004, OR =2.069, 95% CI = 1.262–3.434). When these data were stratified by apolipoprotein E (APOE) ε4 status, the observed association was confined to APOE ε4 non-carriers (additive model: P=0.048, OR =1.191, 95% CI =1.001–1.417; recessive model: P < 0.001, OR = 2.601, 95% CI =1.519–4.566). Furthermore, meta-analysis after sensitive analysis confirmed that rs9271192 within HLA-DRB1 increased the risk of LOAD (OR = 1.12, 95% CI = 1.08–1.15). To summarize, the C allele in HLA-DRB1 rs9271192 may be an independent risk factor for LOAD.

Detection rate of prostate cancer following biopsy among the northern Han Chinese population: a single-center retrospective study of 1022 cases

BackgroundProstate cancer is known to have ethnic and regional differences. The study aimed to clinically evaluate the detection rate of prostate cancer on transrectal ultrasonography (TRUS)-guided prostate biopsy and analyze its characteristics among the northern Han Chinese population at a single center.MethodsBetween October 2009 and September 2016, a total of 1027 Chinese men, who had undergone TRUS-guided prostate biopsy at Qingdao Municipal Hospital, were retrospectively analyzed. Prostate biopsies were performed in the case of an abnormally elevated serum PSA level, and/or abnormal digital rectal examination (DRE) findings, and/or suspicious prostatic imaging findings.ResultsOf the 1022 men enrolled in the analysis, 438 patients (42.8%) were diagnosed with prostate adenocarcinoma histologically. When serum PSA levels were divided into five subgroups (less than 4.0, 4.0 to 10.0, 10.0 to 20.0, 20.0 to 100.0, and ≥ 100.0 ng/ml), the detection rates of prostate cancer were 12.4, 15.9, 34.1, 66.2, and 93.8%, respectively. With serum PSA levels of 4.0 to 10.0 ng/ml, the cancer detection rates for a normal DRE and a suspect DRE finding were 13.5 and 58.2%, respectively. Accordingly, the cancer detection rates for a normal imaging and a suspect imaging finding were 13.5 and 58.2%, respectively. Besides, a large proportion of the patients were in the clinically advanced stage.ConclusionsThe present study data reported a relatively higher prostate cancer detection rate of 42.8% and that the majority of the patients presented with clinically advanced prostate cancers within a local clinical urologic practice. An early detection and screening program for prostate cancer is of great need to reduce the burden from this disease among the northern Han Chinese population.

Association between mitochondrial DNA variations and schizophrenia in the northern Chinese Han population.

To determine whether mitochondrial DNA (mtDNA) variations are associated with schizophrenia, 313 patients with schizophrenia and 326 unaffected participants of the northern Chinese Han population were included in a prospective study. Single-nucleotide polymorphisms (SNPs) including C5178A, A10398G, G13708A, and C13928G were analyzed by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Hypervariable regions I and II (HVSI and HVSII) were analyzed by sequencing. The results showed that the 4 SNPs and 11 haplotypes, composed of the 4 SNPs, did not differ significantly between patient and control groups. No significant association between haplogroups and the risk of schizophrenia was ascertained after Bonferroni correction. Drawing a conclusion, there was no evidence of an association between mtDNA (the 4 SNPs and the control region) and schizophrenia in the northern Chinese Han population.

Genetic Polymorphism of LBX1 Is Associated With Adolescent Idiopathic Scoliosis in Northern Chinese Han Population.

A case-control association study was performed to investigate the relationship between ladybird homeobox (LBX1) and adolescent idiopathic scoliosis (AIS) in northern Chinese Han population. To explore the prevalence and functional importance of LBX1 polymorphisms in patients with AIS within the northern Chinese Han population. AIS is the most common subtype of idiopathic scoliosis. Genetic factors such as LBX1 polymorphisms have been recently proved to be associated with AIS in some populations. In this study we explored the prevalence and functional importance of the polymorphisms around LBX1 in patients with AIS within the northern Chinese Han population. Five tag single nucleotide polymorphisms (SNPs) around or in LBX1 were genotyped in 180 patients with AIS and 182 controls. And the luciferase assay was performed to explore the functional importance of the most significant SNPs. We replicated that rs11190870, previously reported as the most significantly associated SNP, was enriched in our AIS cohort. In addition, we found that the T allele of rs1322331 was associated with a novel risk allele (odds ratio = 3.349, 95% confidence interval 1.742-6.436). In the following luciferase assay, the TT-type promoter showed significantly reduced transcription activity in vitro. Two SNPs around LBX1, rs11190870 and rs1322331 are associated with AIS in northern Chinese Han population. The T allele of rs1322331 is a novel risk allele. We hypothesize that rs1322331 might increase patients' susceptibility to AIS by reducing LBX1-AS1 transcription and thus upregulating the function of LBX1. 3.

Novel CD137 Gene Polymorphisms and Susceptibility to Ischemic Stroke in the Northern Chinese Han Population.

Ischemic stroke is a leading cause of mortality and morbidity worldwide, and atherosclerosis is one of the major risk factors for this neurologic deficit. Recent studies have revealed the important role of CD137 in human atherosclerosis. Here, we analyzed the association of CD137 single nucleotide polymorphisms (SNPs) with ischemic stroke. We assessed three SNPs (rs161827, rs161818, and rs161810) of the CD137 gene and their association with ischemic stroke in a northern Chinese Han population. A total of 496 ischemic stroke patients and 486 gender-matched control subjects were genotyped. We classified these patients according to complications with diabetes and hypertension and also by ischemic stroke subtypes. Allele, genotype, and haplotype association studies were tested in all patients and subgroups. We used multivariable logistic regression analysis combined with 10,000 permutations to analyze the association of CD137 polymorphisms with ischemic stroke. After adjusting for relevant factors, rs161827 was significantly different between patients with and without diabetes and the control group (p=0.0001, p=0.014, and p=0.0001, respectively). In addition, rs161818 and rs161810 differed significantly between patients without diabetes and the control subjects (p=0.0001 and p=0.004, respectively). rs161827, rs161818, and rs161810 were all statistically significant among the combination stroke subgroup compared with the controls. These results indicate that the CD137 gene is associated with risk of ischemic stroke in the northern Han Chinese. Moreover, CD137 gene polymorphism may be one mediating factor between diabetes and ischemic stroke.

Gas6 gene rs8191974 and Ap3s2 gene rs2028299 are associated with type 2 diabetes in the northern Chinese Han population

Previous studies in other countries have shown that single nucleotide polymorphisms (SNPs) in the growth arrest-specific gene 6 (Gas6; rs8191974) and adapter-related protein complex 3 subunit sigma-2 (Ap3s2; rs2028299) were associated with an increasedrisk for type 2 diabetes mellitus (T2DM). However, the association of these loci with T2DM has not been examined in Chinese populations. We performed a replication study to investigate the association of these susceptibility loci with T2DM in the Chinese population.We genotyped 1968 Chinese participants (996 with T2DM and 972controls) for rs8191974 in Gas6 and rs2028299 near Ap3s2, and examined their association with T2DM using a logistic regression analysis. We also analyzed the correlation of genotypes and clinical phenotypes. The distribution of the T allele of SNP rs8191974 in the Gas6 gene was significantly different between T2DM cases and controls when compared with the C allele (P<0.05, OR: 0.80, 95% CI: 0.69-0.94). The occurrence of the CT genotype and the dominant model was also significantly less frequent in the T2DM cases vs. controls when compared with the CC genotype (CT vs. CC: P<0.05, OR: 0.75, 95% CI:0.62-0.90; TT+CT vs. CC: P<0.05, OR:0.75, 95% CI:0.63-0.90). In SNP rs2028299, the allele C showed no statistically significant differencein distribution between the control and T2DM groups when compared with allele A. However, in male populations, the dominant model was statistically more frequent when compared with genotype AA (CC+CA vs. AA: P<0.05, OR:1.29, 95% CI:1.02-1.64), and in obesity-stratified analysis, we also observed a significant difference in the distribution of the dominant model between the T2DM cases and controls in subjects with BMI≥24 kg/m2 and BMI<28kg/m2 (CC+CA vs. AA: P<0.05, OR: 6.33, 95% CI:4.17-9.61). In conclusion, our study shows that SNPsrs8191974 and rs2028299 are significantly associated with T2DM in the Chinese population.

Association of SAA gene polymorphism with ischemic stroke in northern Chinese Han population

BackgroundSerum amyloid A protein (SAA) is known as an inflammatory factor and an apolipoprotein that can replace apolipoprotein A-I/II components as the major apolipoprotein of high-density lipoprotein (HDL), which is related to atherosclerosis. The present study is aimed to evaluate whether the SAA gene polymorphism is involved in ischemic stroke in northern Chinese Han population. MethodsIn a case-control study, the participants included 396 patients (239 males, 157 females) with ischemic stroke and 360 healthy subjects (211 males, 149 females). The rs12218 polymorphism of the SAA gene was analyzed by polymerase chain reaction and restriction fragment length polymorphism, while the rs2468844 polymorphism of the SAA gene was analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. ResultsThe frequencies of the CC genotype and the C allele of rs12218 were higher in participants with ischemic stroke than in the control group (P=0.020 in males, P=0.001 in large-artery atherosclerosis group, LAA). The frequencies of the AG genotype and the G allele of rs2468844 were higher in participants with ischemic stroke than in the control group (P=0.040 in males, P=0.011 in large-artery atherosclerosis group). Multiple logistic regression analysis revealed the significance of the rs12218 in males and in large-artery atherosclerosis group after adjustment for confounding factors. ConclusionThe rs12218 polymorphism of the SAA gene was associated with ischemic stroke in males and in patients with large-artery atherosclerosis group in northern Chinese Han population.

The association between apolipoprotein A1-C3-A5 gene cluster promoter polymorphisms and risk of ischemic stroke in the northern Chinese Han population.

ObjectiveGiven its effects on lipid metabolism, the apolipoprotein A1-C3-A5 (APOA1-C3-A5) gene cluster is thought to play an important role in ischemic stroke pathogenesis. Here, we evaluated whether the APOA1-C3-A5 cluster is associated with ischemic stroke in the northern Chinese Han population.MethodsThis case–control study analyzed 812 patients with ischemic stroke and 844 healthy controls with regard to four APOA1-C3-A5 cluster promoter single nucleotide polymorphisms (SNPs), rs670, rs2854116, rs2854117, and rs662799, using the SNaPshot Multiplex sequencing assay. Potential associations among ischemic stroke, genotyping, and allele frequencies were assessed.ResultsAPOA1 rs670 CT/TT genotypes, APOA5 rs662799 AG/GG genotypes, and the APOC3 rs2854116 CC genotype were associated with an increased risk of ischemic stroke according to multivariate logistic analysis after adjusting for confounding factors. A significantly increased risk for ischemic stroke was also identified among high-risk haplotypes (C-C-T-A and T-T-C-A) for rs670–rs2854116–rs2854117–rs662799.ConclusionThis study showed that rs670, rs2854116, and rs662799 SNPs of the APOA1-C3-A5 cluster are associated with ischemic stroke in the northern Chinese Han population.

Decreased human leukocyte antigen A*02:01 frequency is associated with risk of glioma and existence of human cytomegalovirus: a case-control study in Northern China.

Human leukocyte antigens (HLAs) play an important role in host defense against viral infection and tumorigenesis. Human cytomegalovirus (HCMV) has been linked to glioma development. This study investigated the relationship between HLA distribution, presence of HCMV, and glioma development in a Han Chinese population. The study population included 150 glioma patients and 150 tumor-free brain injury control subjects (control-A) matched according to geography, ethnicity, age, and gender. HLA allele frequency was compared between the two groups using peripheral blood samples by PCR sequence-based typing. These data were also compared with HLA frequencies obtained from a Northern Chinese Han population database (control-B). HCMV DNA was detected in the peripheral blood of glioma patients and control group-A by nested PCR. The expression of HCMV proteins IE1-72 and pp65 in tumor tissues was evaluated by immunohistochemistry. The frequency of HLA-A*02:01 was decreased in glioma patients as compared to control group-A and -B (P<0.001 and P=0.001, respectively). The age/sex-adjusted odds ratio for HLA-A*02:01 positivity vs. negativity was 0.392 (95% confidence interval 0.225-0.683). HCMV was more frequently detected in the peripheral blood and tumor tissue of HLA-A*02:01-negative glioma patients. HLA-A*02:01 and HCMV were not associated with overall survival. There is a correlation between decreased HLA-A*0201 allele frequency and glioma susceptibility.

Correlations of TNF-α gene promoter polymorphisms with the risk of thymoma-associated myasthenia gravis in a northern Chinese Han population.

This study was performed with the aim to investigate the correlations of tumor necrosis factor-alpha (TNF-α) gene promoter polymorphisms with the risk of thymoma-associated myasthenia gravis (T-MG) in a northern Chinese Han population. Between June 2005 and June 2015, 305 MG patients (150 males and 155 females, MG group) and 293 healthy volunteers (negative control (NC) group) were enrolled in this study. Among the MG patients, there were 121 patients with thymoma-associated MG (T-MG group) and 184 without T-MG (NT-MG group). Enzyme-linked immunosorbent assay (ELISA) was used for the serum TNF-α level. Polymerase chain reaction-restriction fragment length polymorphism was conducted to determine genotype and allele frequencies of TNF-α gene promoter -1031T/C, -857C/T and -863C/A. The haplotype was analyzed with the SHEsis software. Logistic regression analysis was performed for correlations between TNF-α gene promoter polymorphisms and the risk of T-MG. The T-MG group had higher frequencies of the CT/TT genotype and T allele of -857C/T than the NT-MG and NC groups. The frequencies of the CC genotype and C allele of -1031T/C were higher in the T-MG group than in the NT-MG and NC groups, and higher in male patients in the T-MG group than in male patients in the NC group. TTA and TTC haplotypes exhibited lower frequencies in the T-MG group than in the NT-MG group. The ocular MG patients exhibited lower frequencies of the TT genotype and T allele of -857C/T than the generalized MG patients did. The TNF-α level was elevated in the T-MG group compared with that in the NC and NT-MG groups, indicating that the TC+CC and CT+TT genotypes were increased compared with the TT and CC genotypes in the -1031T/C and -857C/T, respectively. Logistic regression analysis suggested that expressions of anti-acetylcholine receptor antibodies, Osserman's classification, -1031T/C and -857C/T polymorphisms and the TTA haplotype were the independent risk factors for T-MG. These findings reveal that TNF-α -1031T/C and -857C/T polymorphisms and the TTA haplotype may be correlated with the occurrence of T-MG in a Northern Chinese Han population.

Association between NAT2 polymorphisms and the risk of schizophrenia in a Northern Chinese Han population.

The gene that encodes N-acetyltransferase 2 (NAT2), an enzyme that plays a crucial role in the metabolism of many drugs and xenobiotics, is located on chromosome 8p22, one of the most convictive susceptibility loci of schizophrenia. NAT2 genetic polymorphisms lead to various enzyme acetylation phenotypes. In the present study, six selected NAT2 exonic single nucleotide polymorphisms were genotyped in an independent case-control sample of a Northern Chinese Han population to verify the possible association between NAT2 and schizophrenia. Three (rs1801280T/341C, rs1799930/G590A, and rs1208/A803G) of the six single nucleotide polymorphisms showed significant allele frequency differences between the case and the control groups after rigorous Bonferroni correction. One protective fast-acetylation haplotype (NAT2*4) and two risk slow acetylation haplotypes (NAT2*5B and NAT2*6A) were discovered to be associated with schizophrenia. Our results indicate that NAT2 may be a susceptibility gene for schizophrenia in this Chinese Han population, and the risk haplotypes might cause the impairment of NAT2 in metabolizing neurotoxic substances.

Polymorphic variants in VAX1 and the risk of nonsyndromic cleft lip with or without cleft palate in a population from northern China.

Background:Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common craniofacial birth defects, and the etiology of NSCL/P involves both genetic and environmental factors. Genome-wide association study (GWAS) identified a novel susceptibility locus of ventral anterior homeobox 1 (VAX1) in patients with NSCL/P. However, the association of single nucleotide polymorphisms (SNPs) of VAX1 with NSCL/P is inconclusive due to the differences in the racial and ethnic populations. The aim of this study was to replicate the association between VAX1 and NSCL/P in a northern Chinese Han population.Methods:Our study included 186 patients with NSCL/P and 223 healthy individuals from northern China. Five SNPs (rs4752028, rs10787760, rs7078160, rs6585429, and rs1871345) on VAX1 were genotyped using the SNaPshot method.Results:Recessive genetic model analysis revealed that homozygous genotype CC of VAX1 rs4752028 was associated with an increased risk of NSCL/P (odds ratio = 1.89, 95% confidence interval = 1.12–3.19, P = 0.017), but the results were not significant after the Bonferroni correction for multiple comparisons. The allele and genotype frequencies of rs10787760, rs7078160, rs6585429, and rs1871345 and the allele frequencies of rs4752028 showed no significant differences between cases and controls. Haplotype and SNP-SNP interaction analyses did not detect any significant association of VAX1 with the occurrence of NSCL/P.Conclusion:VAX1 rs4752028 was weakly associated with NSCL/P development in the studied northern Chinese Han population.

Association of single-nucleotide polymorphisms of CDH1 with nonsyndromic cleft lip with or without cleft palate in a northern Chinese Han population.

Background:Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a common congenital malformation among live births, and depends on race and ethnic background. The CDH1 gene plays a vital role in orofacial development. Our research was conducted to examine the association between 3 single-nucleotide polymorphisms in the CDH1 gene and NSCL/P.Methods:Three single-nucleotide polymorphisms (rs16260, rs9929218, and rs1801552) of the CDH1 gene were genotyped using the Snapshot mini-sequencing technique in 331 patients with NSCL/P and 271 controls from the northern Chinese Han population.Results:The investigation indicated that presence of the CDH1 rs1801552 TT genotype under the assumption of a recessive model is related to the decreased risk for NSCL/P (odds ratio 0.53, 95% confidence interval 0.34–0.81, P = 0.003). The results were still significant after the Bonferroni correction for multiple comparisons. However, nonsignificant differences in rs16260 and rs9929218 were found between cases and controls.Conclusion:Our study demonstrates that the CDH1 polymorphisms were significantly associated with the risk of NSCL/P in the northern Chinese Han population. We provide further evidence regarding the role of CDH1 variations in the development of NSCL/P in a northern Chinese Han population.

Association of the FADS gene cluster with coronary artery disease and plasma lipid concentrations in the northern Chinese Han population

We investigated the association of single nucleotide polymorphisms (SNPs) in the fatty acid desaturase (FADS) gene cluster with coronary artery disease (CAD) in a case-control study and evaluated the possible influence of genetic variation on total cholesterol (TC) and triglyceride concentrations in the controls. In total, 497 CAD patients and 495 unrelated controls were genotyped for eight SNPs in the FADS gene cluster, and the blood lipid levels of subjects were measured. Three genetic models, including codominant, dominant and recessive, were used to analyze the genotypic relationship with CAD and plasma lipid levels. Single locus genotypic analysis revealed that rs1000778 in FADS3 under a recessive model (AA vs. GG-GA) was significantly associated with CAD adjusted for risk factors. The rs1000778 minor allele AA was associated with a lower risk of CAD (OR =0.37, 95% CI: 0.15–0.89, P=0.025). In the control group, there were significant differences in TC concentrations under a recessive genetic model for rs174575 (C/G) in FADS2 and for rs174450 (A/C) and rs7115739 (G/T) in FADS3 (P=0.053, 0.016 and 0.018, respectively). The rs1000778-G variant in FADS3 may contribute to the susceptibility of CAD, but the result needs to be further confirmed because of small sample size in our study. Genetic variations in FADS2 and FADS3 influence TC concentration in the northern Chinese Han population.