Northern Chinese Han Population Research Articles

Association of a COL1A1 Gene Haplotype with Pathologic Myopia in a Northern Chinese Han Population

To investigate the relationship between COL1A1 variations and the susceptibility to pathologic myopia (PM) among the general population in Northern China, we included 525 PM patients and 1105 non-myopic controls. All PM patients underwent comprehensive ophthalmologic examinations. DNA was extracted from peripheral venous blood samples and genotyped using the MassArray System. Statistical analyses, including Hardy-Weinberg equilibrium, χ2 test, and linkage disequilibrium analysis, were conducted to compare the genotypic and allelic distributions of SNPs between PM patients and controls. The results showed no significant differences in the genotypic and allelic distributions of rs2075555, rs2269336, and rs1107946 between the PM and control groups. However, haplotype analysis revealed that the G-G-C and T-C-A haplotypes are risk factors for PM (G-G-C: OR = 1.399, 95% CI = 1.206–1.623, P < 0.001, Pc < 0.001; T-C-A: OR = 1.248, 95% CI = 1.064–1.456, P = 0.007, Pc = 0.021). Although individual SNPs in COL1A1 were not significantly associated with PM, specific haplotypes (G-G-C and T-C-A) were identified as risk factors. This suggests a potential role of COL1A1 in the development of PM.

An epigenome-wide association study of waist circumference in Chinese monozygotic twins.

Central obesity poses significant health risks because it increases susceptibility to multiple chronic diseases. Epigenetic features such as DNA methylation may be associated with specific obesity traits, which could help us understand how genetic and environmental factors interact to influence the development of obesity. This study aims to identify DNA methylation sites associated with the waist circumference (WC) in Northern Han Chinese population, and to elucidate potential causal relationships. A total of 59 pairs of WC discordant monozygotic twins (ΔWC >0) were selected from the Qingdao Twin Registry in China. Generalized estimated equation model was employed to estimate the methylation levels of CpG sites on WC. Causal relationships between methylation and WC were assessed through the examination of family confounding factors using FAmiliaL CONfounding (ICE FALCON). Additionally, the findings of the epigenome-wide analysis were corroborated in the validation stage. We identified 26 CpG sites with differential methylation reached false discovery rate (FDR) < 0.05 and 22 differentially methylated regions (slk-corrected p < 0.05) strongly linked to WC. These findings provided annotations for 26 genes, with notable emphasis on MMP17, ITGA11, COL23A1, TFPI, A2ML1-AS1, MRGPRE, C2orf82, and NINJ2. ICE FALCON analysis indicated the DNA methylation of ITGA11 and TFPI had a causal effect on WC and vice versa (p < 0.05). Subsequent validation analysis successfully replicated 10 (p < 0.05) out of the 26 identified sites. Our research has ascertained an association between specific epigenetic variations and WC in the Northern Han Chinese population. These DNA methylation features can offer fresh insights into the epigenetic regulation of obesity and WC as well as hints to plausible biological mechanisms.

Age Estimation by Machine Learning and CT-Multiplanar Reformation of Cranial Sutures in Northern Chinese Han Adults.

To establish age estimation models of northern Chinese Han adults using cranial suture images obtained by CT and multiplanar reformation (MPR), and to explore the applicability of cranial suture closure rule in age estimation of northern Chinese Han population. The head CT samples of 132 northern Chinese Han adults aged 29-80 years were retrospectively collected. Volume reconstruction (VR) and MPR were performed on the skull, and 160 cranial suture tomography images were generated for each sample. Then the MPR images of cranial sutures were scored according to the closure grading criteria, and the mean closure grades of sagittal suture, coronal sutures (both left and right) and lambdoid sutures (both left and right) were calculated respectively. Finally taking the above grades as independent variables, the linear regression model and four machine learning models for age estimation (gradient boosting regression, support vector regression, decision tree regression and Bayesian ridge regression) were established for northern Chinese Han adults age estimation. The accuracy of each model was evaluated. Each cranial suture closure grade was positively correlated with age and the correlation of sagittal suture was the highest. All four machine learning models had higher age estimation accuracy than linear regression model. The support vector regression model had the highest accuracy among the machine learning models with a mean absolute error of 9.542 years. The combination of skull CT-MPR and machine learning model can be used for age estimation in northern Chinese Han adults, but it is still necessary to combine with other adult age estimation indicators in forensic practice.

Association between FOXP3 polymorphisms and expression and neuromyelitis optica spectrum disorder risk in the Northern Chinese Han population.

Forkhead box P3 (FOXP3) plays a critical role in the pathogenesis of autoimmune disorders. In the present study, we genotyped three single-nucleotide polymorphisms, namely, rs2232365, rs3761548, and rs3761549, to determine the relationship between FOXP3 polymorphisms and neuromyelitis optica spectrum disorder (NMOSD) susceptibility among the Northern Chinese Han population. We genotyped single nucleotide polymorphisms at loci of the FOXP3 gene (rs2232365, rs3761548, and rs3761549136) in 136 NMOSD patients and 224 healthy subjects using the multiplex SNaPshot technique. Allele, genotype, and haplotype frequencies were compared. qPCR was used to analyze the mRNA expression levels of FOXP3 in the peripheral blood mononuclear cells of 63 NMOSD patients and 35 healthy subjects. Non-parametric tests were used to test the FOXP3 mRNA expression across the different groups. The minor allele frequency (MAF) of G in rs2232365 was markedly lower in the NMOSD group than in the control group (odds ratio [OR] = 0.57, 95% confidence interval [95% CI]: 0.41-0.79, p = 0.001). Using genetic (codominant, dominant, and recessive) models and performing haplotype analyses, the MAF of G in rs2232365 was shown to be associated with protection against NMOSD in this population. Furthermore, haplotype analysis revealed that the haplotype GCT and the rs2232365, rs3761548, and rs3761549 alleles predicted protection against NMOSD (OR = 0.63, 95% CI = 0.41-0.97, p = 0.038). The proportions of the three genotypes of rs2232365 (p = 0.001) were not significantly different between the moderate-to-severe (Expanded Disability Status Scale (EDSS) ≥ 3 points) and mild (EDSS < 3 points) groups. Evidently, the proportion of patients with the AA genotype (64.3%) among the rs2232365 patients was significantly greater in the moderate-to-severe group than in the mild group (36.4%). However, the proportion of patients with the GG genotype (15.2%) among the rs2232365 patients was significantly greater in the mild group than in the moderate-to-severe group (2.9%). The mRNA expression of FOXP3 was markedly greater in the NMOSD group than in the control group (p = 0.001). Nevertheless, acute non-treatment patients exhibited lower FOXP3 mRNA expression than healthy controls and patients in the remission group (p = 0.004 and 0.007, respectively). FOXP3 polymorphisms and haplotypes are related to NMOSD susceptibility among the Han Chinese population. The minor allele G of FOXP3 rs2232365 and the haplotype GCT are associated with protection against NMOSD. The GG genotype may decrease the severity of NMOSD, whereas the AA genotype is related to moderate-to-severe NMOSD. FOXP3 mRNA expression is greater in patients with NMOSD than in healthy controls. However, it is decreased in acute non-treatment patients compared with healthy controls.

Performance and characterization of 94 identity-informative SNPs in Northern Han Chinese using ForenSeq ™ DNA signature prep kit

Target and flanking region (FR) variation at 94 identity-informative SNPs (iSNPs) are investigated in 635 Northern Han Chinese using the ForenSeq DNA Signature Prep Kit on the MiSeq FGx Forensic Genomics System. The dataset presents the following performance characteristics (average values): ≥60% bases with a quality score of 20 or higher (%≥ Q20); >700 × of depth of coverage (DoC) from both Sample Details Reports and Flanking Region Reports; >80% of effective reads; ≥60% of allele coverage ratio (ACR); and ≥70% of inter-locus balance, while some stable low-performance characteristics are also observed: low DoC at rs1736442, rs1031825, rs7041158, rs338882, rs2920816, rs1493232, rs719366, and rs2342747; high noise at rs891700; and imbalanced ACR at rs6955448 and rs338882. The average amplicon length is 69 bp, suitable for detecting degraded samples. Bioinformatic concordance achieves 99.99% between the ForenSeq Universal Analysis Software (UAS) and the Integrative Genomic Viewer (IGV) inspection. Discordance results from flanking region deletions of rs10776839, rs8078417, rs2831700, and rs1454361. Due to FR variants within amplicons detected by massively parallel sequencing (MPS), the increases in the number of unique alleles, effective alleles (Ae), and observed heterozygosity (Hobs) are 46.81%, 4.51%, and 3.29%, respectively. Twelve FR variants are first reported to dbSNP, such as rs1252699848, rs1665500714, rs1771121532, rs2097285015, rs1851671415, rs2045669877, rs2046758811, rs2044248635, rs1251308240, rs1968822112, rs1981638299, and rs1341756746. All 94 iSNPs from target and amplicon data are in Hardy-Weinberg equilibrium (HWE) and independent within autosomes. As expected, forensic parameters from the amplicon data increase significantly on the combined power of discrimination (CPD = 1 – 3.9876 × 10−38) and the combined power of exclusion (CPE = 1 – 6.6690 × 10−8). Additionally, the power of the system effectiveness (CPD = 1 − 6.7054 × 10−72 and CPE = 1 − 4.4719 × 10−20) with sequence-based 27 autosomal STRs and 94 iSNP amplicons in combination is substantially improved compared to one type of marker alone. In conclusion, we have established a traditional length-based and current sequence-based reference database with 58 STRs and 94 iSNPs in the Northern Han Chinese population. We hope these data can serve as a solid reference and foundation for forensic practice.

The SNTB1 and ZFHX1B gene have susceptibility in northern Han Chinese populations with high myopia

The aim of this study was to explore the association between SNTB1 and ZFHX1B polymorphisms and high myopia (HM) in a Northern Han Chinese population. This case-control study included 457 HM and 860 healthy subjects from the Northern Han Chinese population. Four single nucleotide polymorphisms (SNPs) (rs7839488, rs4395927, rs4455882, and rs6469937) in SNTB1 and one SNP in ZFHX1B (rs13382811)were selected based on two previous genome-wide association study (GWAS) studies. The allele and genotype distributions of SNPs in SNTB1 and ZFHX1B were compared between the two groups using the chi-square test. The allele results were adjusted for age and sex using Plink software (Plink 1.9). Pairwise linkage disequilibrium (LD) and haplotype analyses were performed using SHEsis software. For HM subjects, the mean age was 44.80 ± 17.11 years, and for the control subjects, it was 44.41 ± 14.26 years. For rs7839488 of the SNTB1 gene, the A allele is a risk allele and the G allele is a wild allele. The A allele had no statistical significance with the HM cases and controls (OR = 0.90, 95% CI = 0.74–1.09, aP = 0.273, Pc = NS). There was a LD in SNTB1 (rs7839488, rs4395927, rs4455882, and rs6469937). The G-C-A-G haplotype frequency was higher in HM subjects than that of the controls (OR = 1.31, 95% CI = 1.07–1.60, P = 0.008). Meanwhile, the A-T-G-A haplotype frequency was slightly lower in the HM group (OR = 0.81, 95% CI = 0.66–0.99, P = 0.048). In the ZFHX1B gene, the frequency of the minor T allele of rs13382811 was significant higher in the HM group than in the control group (OR = 1.34, 95% CI = 1.11–1.61, aP = 0.001, Pc = 0.009). Furthermore, compared to the CC genotype, there were significant differences in the CT genotype (OR = 1.57, 95% CI = 1.23–2.00, aP < 0.001, Pc = 0.002). In conclusion, G-C-A-G is a risk haplotype from the SNTB1 gene in high myopia patients. The minor T-allele of ZFHX1B rs13382811 is a risk factor for high myopia. SNTB1 and ZFHX1B are both risk genes associated with increased susceptibility to high myopia in the Northern Han Chinese population.

Association study of WNK1 genetic variants and essential hypertension risk in the Northern Han Chinese in Beijing.

Background: Essential hypertension (EH) is a complex disorder resulting from interaction of genetic and environmental factors. Lysine deficient protein kinase 1 (WNK1) plays a very important role in maintaining renal potassium, sodium and chlorine ions balance as well as the regulation of blood pressure, so the WNK1 gene is considered a key gene for EH. This study thus sought to evaluate possible genetic associations between the WNK1 genetic variants and EH risk in the Northern Han Chinese population in Beijing. Methods: This study included 476 hypertensive subjects and 491 normotensive subjects. A total of 12 tag SNVs of WNK1 gene were genotyped successfully by TaqMan assay. Comparisons of the genotypic and allelic frequency between cases and controls were made by using the chi-square test. Logistic regression analyses were performed under different genetic models, and haplotype analysis was also conducted. Results: A total of 12 SNVs were identified as the tag SNVs for WNK1 gene. Significant associations were observed between WNK1 gene rs7305099 variant and EH risk, and T allele influenced hypertension risk in a protective manner. After correcting for multiple testing using Bonferroni, the significance remained for the SNV of rs7305099 in three genetic models [allele comparison, p < 0.0002, OR = 0.627, 95%CI (0.491-0.801); homozygote comparison, p < 0.0003, OR = 0.278, 95%CI (0.140-0.552); additive model, p < 0.0003, OR = 0.279, 95%CI (0.140-0.553)]. In the haplotype analyses, we found that the haplotype A-A-A-C-G-G-G was significantly associated with increased risk for EH (p = 0.043, OR = 1.23). Conclusion: Our data suggested that the rs7305099 genetic variant and the haplotype A-A-A-C-G-G-G on WNK1 gene might be associated with the susceptibility of EH in the Northern Han Chinese population. These could provide evidences to the risk assessment, early prevention and individualized therapy of EH to some extent.

CD33 polymorphisms and Parkinson’s disease Parkinson’s disease in northern Chinese Han population: A case-control study

ObjectiveParkinson's disease (PD) represents the multisystem illness involving immunological and neuroinflammatory dysfunction. The present work focused on evaluating link of CD33 single nucleotide polymorphisms (SNPs) with PD vulnerability of the northern Chinese Han people, considering CD33’s role as a critical immunoregulatory receptor in neuroinflammatory responses. MethodsThe present case-control study included 475 PD cases together with 475 normal controls. A further division of PD patients into two categories was made: 74 patients with early-onset PD (EOPD; onset age ≤ 50 years) and 401 patients with late-onset PD (LOPD; onset age > 50 years). DNA extraction was conducted, followed by genotyping for 2SNPs of CD33 polymorphisms with polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP). ResultsAlleles (G vs. A, P = 0.028) and AA genotypes (P = 0.042) of rs12985029 were significantly different between the groups. Distinctions were observed between the two groups in the recessive, co-dominant, and additive models (nominal P = 0.030, nominal P = 0.045, and P = 0.032). AA genotype frequency among male PD was higher compared to corresponding male controls (P = 0.034), and in the male group allele A was a factor causing the disease (P = 0.026). The rs12985029 genotypes and allele frequency were different in EOPD compared with LOPD (P = 0.002, P = 0.002, respectively), and in LOPD group relative to healthy control group (P = 0.020 and P = 0.004, separately). Regarding the rs3826656 polymorphism, the frequency of GA genotype was higher in the control group than in the case group (nominal P = 0.036). Overdominance and co-dominant models were different between these groups (P = 0.026, nominal P = 0.030). Subgroup analysis revealed genotype frequency differences between rs3826656 LOPD group and control group (P = 0.018). Furthermore, relationship between rs3826656 and rs12985029 (D' = 0.162, r2 = 0.021) did not reach a complete level of linkage disequilibrium (LD) of northern Chinese Han people. ConclusionThis study establishes an association between CD33 rs12985029 and rs3826656 polymorphisms and PD risk among the selected northern Chinese Han people. The GA genotype, rs3826656, may act as a protective factor against PD, while the A allele, rs12985029,could be genetic risk factor related to PD. Future research should include larger sample sizes and other human populations to further investigate how CD33 polymorphisms contribute to PD.

Mitofusin-2 gene polymorphisms and metabolic dysfunction associated fatty liver disease: a case-control study in a Chinese population

Objectives Mitofusion-2 (Mfn2) may have a role in mitochondrial oxidative stress and insulin resistance that can promote the development of metabolic dysfunction associated fatty liver disease (MAFLD). This retrospective and case control study aimed to explore the relationships between common Mfn2 single nucleotide polymorphisms (SNPs) and MAFLD in a northern Han Chinese population. Methods Six Mfn2 SNPs (rs2336384, rs873458, rs873457, rs4846085, rs2878677, and rs2236057) were genotyped using the ligase detection reaction in 466 MAFLD patients and 423 healthy controls. Genotype and allele frequencies were calculated, along with haplotype analysis and pairwise linkage disequilibrium. Results The genotype distribution of rs2336384, rs2878677, and rs2236057 among the MAFLD patients showed a significantly different pattern from that of healthy controls. The data showed that an increased risk of MAFLD was significantly correlated with patients carrying the GG genotype of rs2336384, CC genotype of rs873457, TT genotype of rs4846085, TT genotype of rs2878677, and the AA genotype of rs2236057. Moreover, The GGCTTA haplotype was found to be adversely linked with MAFLD by haplotype analysis. Conclusion The current findings suggest a strong link between certain Mfn2 gene polymorphisms and MAFLD.

Reference intervals for LC-MS /MS measurements of plasma renin activity, aldosterone, angiotensin II, and 24-hour urinary aldosterone in Northern Chinese Han population

BackgroundExamination of aldosterone to Renin Ratio (ARR) and plasma aldosterone concentration (PAC) or 24-h urinary aldosterone excretion (24-h UALD) was the necessary tests in confirmatory tests for primary aldosteronism (PA). We developed a combined liquid chromatography-tandem mass spectrometry method (LC-MS/MS) for plasma renin activity (PRA), PAC, and angiotensin II (Ang II) and investigated their reference intervals (RIs) in northern Chinese Han population. The RIs of 24-h UALD excretion were also studied using LC-MS/MS. MethodsA total of 309 healthy volunteers were recruited in 3 cities in China. PRA, PAC, Ang II, and 24-h UALD were measured using the laboratory-developed LC-MS/MS. Multiple linear regression and the variance component model were applied to determine if the RI needed to be split. The RIs of PRA, PAC, and Ang II were determined using the nonparametric percentile method. ResultsThe laboratory-developed LC-MS/MS method was verified and showed good performance. Standard deviation ratio (SDR) sex for PAC and SDR region for Ang II are 0.466 and 0.407, respectively, indicating that the RIs of PAC and Ang II must be divided by sex and region, respectively. In addition, the SDR 24hUK for 24-h UALD is 0.579, indicating that the RI of 24-h UALD must be partitioned by urine potassium. ConclusionRIs were established for tests related to the renin-angiotensin-aldosterone system in the apparently healthy northern Chinese Han population by the LC-MS/MS method.

Genetic variation within the pri-let-7f-2 in the X chromosome predicting stroke risk in a Chinese Han population from Liaoning, China: From a case-control study to a new predictive nomogram.

Stroke is the most common cause of disability and the second cause of death worldwide. Therefore, there is a need to identify patients at risk of developing stroke. This case-control study aimed to create and verify a gender-specific genetic signature-based nomogram to facilitate the prediction of ischemic stroke (IS) risk using only easily available clinical variables. A total of 1,803 IS patients and 1,456 healthy controls from the Liaoning province in China (Han population) were included which randomly divided into training cohort (70%) and validation cohort (30%) using the sample function in R software. The distribution of the pri-let-7f-2 rs17276588 variant genotype was analyzed. Following genotyping analysis, statistical analysis was used to identify relevant features. The features identified from the multivariate logistic regression, the least absolute shrinkage and selection operator (LASSO) regression, and univariate regression were used to create a multivariate prediction nomogram model. A calibration curve was used to determine the discrimination accuracy of the model in the training and validation cohorts. External validity was also performed. The genotyping analysis identified the A allele as a potential risk factor for IS in both men and women. The nomogram identified the rs17276588 variant genotype and several clinical parameters, including age, diabetes mellitus, body mass index (BMI), hypertension, history of alcohol use, history of smoking, and hyperlipidemia as risk factors for developing IS. The calibration curves for the male and female models showed good consistency and applicability. The pri-let-7f-2 rs17276588 variant genotype is highly linked to the incidence of IS in the northern Chinese Han population. The nomogram we devised, which combines genetic fingerprints and clinical data, has a lot of promise for predicting the risk of IS within the Chinese Han population.

A functional polymorphism of microRNA-143 is associated with the risk of type 2 diabetes mellitus in the northern Chinese Han population.

ObjectiveTo explore the association between two polymorphisms of microRNA-143 (miR-143) and the risk of type 2 diabetes mellitus (T2DM) in the northern Chinese Han population.Study DesignThis case–control study involved 326 patients with T2DM and 342 healthy controls. Two genetic variants (rs4705342 and rs353292) of miR-143 were genotyped by the polymerase chain reaction/ligase detection reaction (PCR-LDR) method. The levels of miR-143 in the serum from 52 T2DM patients and 55 healthy subjects were investigated by quantitative real-time PCR (qRT–PCR).ResultsThe CC genotype frequency of rs4705342 was significantly higher in the T2DM patients than in the healthy controls (P = 0.012). After adjusting for sex, age, and body mass index, the rs4705342 CC genotype was also related to a significantly increased risk of T2DM compared with the TT genotype (adjusted OR: 1.87; 95% CI = 1.09-3.19; P = 0.022). Stratified analyses demonstrated that T2DM patients with the rs4705342 CC genotype had significantly higher levels of low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), and glycated haemoglobin (HbA1C) than those carrying the rs4705342 TT genotype. The qRT–PCR results showed that the expression levels of miR-143 were significantly higher in the serum of cases than in the serum of controls (P < 0.001). Furthermore, the levels of miR-143 were significantly higher in the serum of T2DM patients carrying the rs4705342 CC genotype than in those carrying the TC and TT genotypes of rs4705342 (P = 0.005 and 0.003, respectively).ConclusionThe CC genotype of rs4705342 might be a risk factor for developing T2DM by increasing the expression of miRNA-143 in the northern Chinese Han population.

Application of the Amyloid/Tau/Neurodegeneration Framework in Cognitively Intact Adults: The CABLE Study.

The amyloid/tau/neurodegeneration (AT[N]) framework has conceptualized the Alzheimer's disease (AD) continuum as a continuum of disease with evidence of amyloid-related pathologies independent of clinical manifestation. Based on this framework, it is necessary to reveal the distribution and risk factors of AD continuum in the cognitively intact population among different cohorts and races, including the northern Chinese Han population. This study classified cognitively intact Chinese Alzheimer's Biomarker and LifestylE (CABLE) participants through the AT(N) scheme. Gaussian mixture models were used to identify the cutoff values of cerebrospinal fluid biomarkers, which distinguished AD continuum(A+T-N-,A+T+N-,A+T-N+andA+T+N+) from 1,005 participants (mean age 61 years; 40% female). Multivariable logistic regressions and Cochran-Armitage trend tests were used to test neuropsychological performance and risk factors for AD continuum. Approximately one-third of individuals (33.7%) belonged to the AD continuum. Four potential modifiable risk factors, including hypertension, thyroid diseases, social isolation, and minimal depression symptoms, were identified for the AD continuum (OR ranging 1.68-6.90). A trend toward higher prevalence of the AD continuum was associated with a larger number of risk factors (p for trend <0.0001). The risk of AD continuum increased by approximately twofold for each additional modifiable risk factor (OR 1.9, 95% CI 1.65-2.24, p < 0.0001). This study revealed the distribution and potential risk factors of the AD continuum in a cognitively intact Han population in northern China, which filled the gap in the area about the performance of the AT(N) framework in the Asian population. ANN NEUROL 2022;92:439-450.

Single Nucleotide Polymorphisms of EXOC1, BCL2, CCAT2, and CARD8 Genes and Susceptibility to Cervical Cancer in the Northern Chinese Han Population.

Cervical cancer (CC) is one of the main malignant tumors that threaten the health and lives of women around the world, and its morbidity and mortality rate ranks fourth. At present, most studies on the genetic background of CC focus on genetic polymorphisms. Single nucleotide polymorphisms (SNPs) are considered clinically as potential diagnostic and therapeutic biomarkers for a variety of tumors. Therefore, we aimed to explore the association between SNPs in different genes (EXOC1 gene, BCL2 gene, CCAT2 gene and CARD8 gene) and susceptibility to CC. This study is a case-control study based on women in northern Chinese, which included 492 women with CC and 510 healthy women. This study used multiplex PCR combined with next-generation sequencing to genotype the selected SNPs (rs13117307(C/T) in EXOC1 gene, rs2279115(C/A) in BCL2 gene, rs6983267(G/T) in CCAT2 gene and rs7248320(G/A) in CARD8 gene). The results of the study showed that there was no significant association between the four SNPs and the susceptibility to CC. However, in further stratified analysis, we found that rs13117307 and rs2279115 were significantly related to squamous cell carcinoma antigen (SCC-Ag) levels in women with CC, and rs6983267 was significantly related to the menopausal status of women with CC. Specifically, alleles T of rs13117307 and genoytpe AA of rs2279115 when SCC-Ag is greater than 1.5 ng/ml increase the risk of CC. The genotype TG/TG+TT of rs6983267 increases the risk of CC in premenopausal women. In conclusion, although we did not directly find a significant correlation between four SNPs, rs13117307 in EXOC1 gene,rs2279115 in BCL2 gene, rs6983267 in CCAT2 gene and rs7248320 in CARD8 gene, and CC susceptibility, we found that SNPs rs13117307, rs2279115, rs6983267 were associated with the clinical characteristics of several patients' CC patients. Therefore, this study provides us with new ideas for understanding CC and the diagnosis and treatment of CC in the future.

Role of CD36 rs1761667 AA genotype in the expression of inflammatory cytokines and Parkinson’s disease progression: A case-control study in a northern Han Chinese population

ObjectiveThis study aimed to investigate the effect of CD36 rs1761667 gene polymorphisms on the expression of CD36 and inflammatory cytokines and the progression of Parkinson’s disease (PD). MethodsA total of 138 patients with PD (60 men and 78 women) and 132 healthy controls (48 men and 84 women) from a northern Han Chinese population were enrolled in this case–control study. Polymerase chain reaction–restriction fragment length polymorphism was used to detect the CD36 rs1761667 genotype. An enzyme-linked immunosorbent assay was used to determine the expression of CD36, interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α in the plasma. ResultsThe frequency of the rs1761667 AA genotype was significantly higher in patients with PD than that in healthy controls, suggesting AA genotype to be a risk factor for PD. When compared with those in healthy controls, CD36 levels were significantly lower in patients with PD, whereas IL-6, IL-1β, and TNF-α levels were significantly higher in patients with PD. Furthermore, GA and AA carriers with PD showed lower levels of CD36, and GG, GA, and AA carriers showed higher levels of IL-6, IL-1β, and TNF-α than those in healthy controls. In the PD patient group, AA and GA carriers had lower expression levels of CD36 than GG carriers did, and CD36 levels were lower in AA carriers than in GA carriers. Conversely, AA carriers had elevated expression levels of IL-6 compared with that of GG and GA carriers. Logistic regression analysis revealed that IL-6, IL-1β, and TNF-α levels were risk factors for PD in a northern Han Chinese population. ConclusionThe CD36 rs1761667 AA genotype may increase susceptibility to PD and the expression of inflammatory cytokines.

Association between ABCA7 gene polymorphisms and Parkinson’s disease susceptibility in a northern Chinese Han population

ObjectiveAs a typical member of the ABC transporter superfamily, ABCA7 has been shown to play an important role in stalling the pathogenesis of neurodegenerative disorders through maintaining the normal microglial function, regulating cellular responses to inflammation and ER stress, and modulating lipid metabolism. Variants in the ABCA7 locus have been hypothesized to be correlated with the genetic predisposition of several neurodegenerative disorders. The goal of this study was to examine whether there is a link between three specific single nucleotide polymorphisms in the ABCA7 gene, namely, rs3764650, rs4147929, and rs3752246, with the risk of developing Parkinson’s disease (PD) in a northern Chinese Han community. MethodsIn this case-control study, we recruited 821 participants, including 411 patients with sporadic PD and 410 independent, healthy controls. A Polymerase Chain Reaction-Restriction Fragment Length Polymorphism genotyping assay was used to identify polymorphisms of the three selected single nucleotide polymorphisms (rs3764650, rs4147929, and rs3752246) of the ABCA7 gene. Sanger sequencing was further applied to identify the accuracy of the genotyping results. The chi-square test was used to compare the frequencies of alleles and genotypes in patients and controls. Odds ratios and 95% confidence intervals were calculated using logistic regression. ResultsWe found significant between-group differences in the alleles (A vs. G, nominal P = 0.014) and dominant models (AA + GA vs. GG, nominal P = 0.015) of rs4147929. Subgroup analysis showed that the frequency of the rs4147929 A allele in male patients with PD was significantly higher than that in male controls (nominal P = 0.036). For the rs3752246 polymorphism, the frequency of the G allele was significantly higher in patients with PD than in controls, and the dominant model fit the data best when considering the nominal P-values (nominal P = 0.019, nominal P = 0.033, respectively). Differences in G allele and genotypes frequencies between patients and controls remained significant in women (nominal P = 0.032 for allele, nominal P = 0.015 for genotype), as well as in individuals aged more than 50 years (nominal P = 0.044, nominal P = 0.020, respectively). No significant differences were observed in allele or genotype frequencies between patients with PD and healthy controls for rs3764650. The frequency of the TCG (rs3764650–rs3752246–rs4147929) haplotype was significantly lower in the PD group than in the healthy control group (odds ratio = 0.772; 95% confidence interval = 0.634–0.940; P = 0.011). ConclusionThe rs4147929 polymorphism was significantly associated with PD susceptibility in the northern Chinese Han population. The A allele of rs4147929 was a risk factor for developing PD. The TCG haplotype presented a protective role in the pathogenesis of PD. Further studies using larger sample sizes, considering different clinical and biochemical parameters such as the cognitive status of subjects at the same time, are warranted to better clarify the effects of these common variants on the pathogenesis and development of PD.

Association of PGLYRP2 gene polymorphism and sporadic Parkinson's disease in northern Chinese Han population

Gut inflammation is increasingly corroborated to take part in the pathogenesis of Parkinson’s disease (PD). The PGLYRP2 gene has been proven to increase susceptibility to inflammatory bowel disease (IBD). The present study aimed to explore the genetic relationship between single nucleotide polymorphism (SNP) of the PGLYRP2 gene and the risk of sporadic PD in the Han population of northern China. The genotypes of the rs3813135 T/C, rs733731 C/T and rs892145 A/T polymorphisms of the PGLYRP2 gene in 400 Chinese Han patients with PD and 400 healthy age-and sex-matched individuals were identified by the Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR–RFLP) method. The results showed that the frequency of the rs892145 AT heterozygote significantly differed between the PD and control groups (OR = 1.459, 95%CI = 1.459–1.039, P = 0.029), as well as the early-onset PD and control groups (P = 0.024). The rs3813135 polymorphism yielded only one significant result: C allele was more common in the male PD group than in the male control group (P = 0.045). Conversely, no significant difference in the genotype frequency of rs733731 was found between the PD and control groups. Five common haplotypes were assessed, of which the TTA and TCA haplotypes were related to PD susceptibility. In summary, our results indicated that the PGLYRP2 gene is associated with sporadic PD in the Chinese Han population, in which the rs892145 AT heterozygote might increase the risk of PD and possibly the risk of early-onset PD. Moreover, linkage disequilibrium (LD) analysis showed these three PGLYRP2 polymorphisms has a strong linkage in causing mutations.

Association of nitric oxide synthase 1 adaptor protein gene polymorphisms with schizophrenia in a Chinese Han population.

Introduction:Previous studies have analyzed the association between nitric oxide synthase 1 adaptor protein (NOS1AP) polymorphisms and schizophrenia; however, the results were inconsistent and there was a lack of evidence in a larger sample of Chinese Han population.Subjects and Methods:We decided to determine the association between four NOS1AP single-nucleotide polymorphisms (i.e., rs1858232A/G, rs4531275C/T, rs4657178C/T, and rs6704393C/T) and schizophrenia in northern Chinese Han population (350 patients and 522 controls) using restriction fragment length polymorphism.Results:Between schizophrenia group and healthy group, the genotype and allele frequencies for rs1858232A/G differed significantly (χ2 = 6.256, 4.145; P = 0.044, 0.045), but neither genotype nor allele frequencies of rs4531275C/T differed significantly. The genotype frequencies for rs4657178C/T and rs6704393C/T differed significantly (χ2 = 19.782, 12.683; P < 0.01, P = 0.002) between schizophrenia group and healthy group. In the gender-specific analysis, we found statistically significant difference in genotype frequencies between patients and controls in both subgroups for rs4657178C/T (χ2 = 9.356, 9.585; P = 0.009, 0.008). There was also a significant difference in the genotype frequency between patients and controls in male subgroup for rs6704393C/T (χ2 = 8.800, P = 0.012). In the haplotype analysis, only the TCT haplotype frequency of rs6704393C/T, rs4531275C/T, and rs4657178C/T differed significantly between patients and controls in total population (χ2 = 5.215, P = 0.022).In conclusion:Individuals with G allele of rs1858232A/G and C allele of rs4657178C/T which may be risk factors for schizophrenia should be given more attention, and also to individuals with the TCT haplotype, who are more likely to have schizophrenia. These results provide novel evidence for an association between NOS1AP polymorphisms and schizophrenia.

Fine-Mapping of the Major Histocompatibility Complex Region Linked to Leprosy in Northern China.

Background: Leprosy is a chronic infectious skin and neurological disease, and genetic background is considered to be one of the major factors of risk. The major histocompatibility complex (MHC) region not only affects susceptibility to leprosy but also its development and outcome. Given the complex traits of the MHC region, variants and the potential mechanism by which HLA influences leprosy development need to be further explored. Methods: We extracted previous genome-wide association study data from the Northern Han Chinese population to perform HLA fine-mapping. Using the 1,000 Genome Project Phase 3 dataset as the reference panel, single-nucleotide polymorphisms (SNP), insertion and deletion (INDEL) and copy number variant (CNV) imputation were carried out. HLA classical alleles and amino acids in the MHC region were imputed using the HAN-MHC database. Further stepwise regression analysis was conducted to analyze independent signals of variants related to leprosy. Results: We identified four independent variants: esv3608598, rs7754498, rs3130781 and rs144388449. Among them, esv3608598 is a CNV and the first HLA CNV associated with leprosy risk. SNP annotation using RegulomeDB, HaploReg, and rVarBase showed that three SNPs are likely to affect the pathogenesis of leprosy. Conclusion: In summary, this is the first study to assess the association between HLA CNV and leprosy susceptibility in a Northern Han Chinese population. By fine mapping of the MHC region in this population, our findings provide evidence for the contribution of HLA to leprosy susceptibility.

ACE and ACTN3 Gene Polymorphisms and Genetic Traits of Rowing Athletes in the Northern Han Chinese Population.

This investigation aimed to explore the effects of ACE I/D and ACTN3 R577X gene polymorphisms on specific quantitative variables, including height, weight, arm span, biacromial breadth, forced vital capacity (FVC), FVC/weight, maximal oxygen uptake (VO2max), prone bench pull (PBP), loaded barbell squat (LBS), and 3,000-m run, in 243 Chinese rowing athletes. The ACE and ACTN3 genotypes were obtained for each athlete via polymerase chain reaction on saliva samples, and the genotype frequency was analyzed. The ACE genotype frequency of rowing athletes were 45.8% II, 42.2% ID, and 12% DD for males and 33.6% II, 48% ID, and 18.4% DD for females. There were significant differences in weight in male athletes, PBP in female athletes, and ACE genotypes. A linear regression analysis using PBP and LBS as different dependent variables and ACE genotypes as independent variables based on the ACE I allele additive genetic effect showed a statistical significance in female athletes (p < 0.05). There was a significant difference in the distribution of the three genotypes among male athletes (36.7% XX, 38.5% RX, and 24.8% RR, χ2 = 5.191, df = 2, p = 0.022 < 0.05). There were no significant differences in the distribution of the three genotypes among female athletes (23.8% XX, 47.8% RX, 28.4% RR, χ 2 = 0.24, df = 2, p = 0.619 > 0.05). The ACTN3 gene polymorphism of male rowing athletes was dominated by the ACTN3 577X allele. There were significant differences in the χ 2 test between groups of male athletes. The ACTN3 R577 allele was dominant in female athletes. There were significant differences between PBP and FVC/body weight and ACTN3 genotypes in male athletes by ANOVA, respectively (p < 0.05). A linear regression analysis using FVC and FVC/body weight as dependent variables and ACTN3 genotypes as independent variables based on the ACTN3 577X allele recessive genetic effect showed statistical significance in male athletes (p < 0.05). These results suggested that ACE and ACTN3 gene polymorphisms may be used as biomarkers of genetic traits in Chinese rowing athletes.