Disease In Chinese Han Population Research Articles

LncRNA RP1-276N6.2 Expression and RP1-276N6.2 Gene Polymorphisms Contribute to the Risk of Coronary Artery Disease in Chinese Han Population.

Long noncoding RNAs (lncRNAs) have been implicated in coronary artery disease (CAD) processes. However, the relationship between the gene polymorphisms of lncRNA RP1-276N6.2 as a novel molecule and susceptibility to CAD remains unclear. In our case-control study, 949 CAD patients and 892 healthy controls were genotyped using the TaqMan genotyping assay. The quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay were performed to examine the expression levels of RP1-276N6.2 and SLC22A3(OCT3). We observed that CAD patients had significantly lower RP1-276N6.2 levels than those healthy participants (p < 0.05). Compared to the wild-type genotype, the rs611950 T allele and the rs10499313 AG genotype and G allele significantly increased the premature CAD risk (p = 0.02, p = 0.002, and p = 0.01, respectively), while the rs505000 G allele reduced this risk (p = 0.01); moreover, the rs505000 CG genotype significantly enhanced the delayed CAD risk (p = 0.03), and the rs505000 G allele reduced the expression levels of RP1-276N6.2 and SLC22A3 (p < 0.05 and p < 0.05, respectively). In addition, RP1-276N6.2 positively regulated the mRNA and secreted protein levels of SLC22A3 (p < 0.05). In conclusion, the RP1-276N6.2 gene polymorphisms were closely associated with CAD risk. LncRNA RP1-276N6.2 may be a potential genetic target for CAD early diagnosis and treatment.

Exploration of KIR genes and hematological-related diseases in Chinese Han population

The function of natural killer (NK) cells has previously been implicated in hematopoietic-related diseases. Killer immunoglobulin-like receptors (KIR) play an important role in NK cells after hematopoietic stem cell transplantation. To explore the immunogenetic predisposition of hematological-related diseases, herein, a multi-center retrospective study in China was conducted, analyzing and comparing 2519 patients with hematopathy (mainly, acute lymphoblastic leukemia, acute myeloid leukemia, aplastic anemia, and myelodysplastic syndrome) to 18,108 individuals without known pathology. Genotyping was performed by polymerase chain reaction with specific sequence primers (PCR-SSP). As a result, we discovered four genes including KIR2DL5 (OR: 0.74, 95% CI 0.59–0.93; Pc = 0.0405), 2DS1 (OR: 0.74, 95% CI 0.59–0.93; Pc = 0.0405), 2DS3 (OR: 0.58, 95% CI 0.41–0.81; Pc = 0.0180), and 3DS1 (OR: 0.74, 95% CI 0.58–0.94; Pc = 0.0405) to be protective factors that significantly reduce the risk of aplastic anemia. Our findings offer new approaches to immunotherapy for hematological-related diseases. As these therapies mature, they are promising to be used alone or in combination with current treatments to help to make blood disorders a manageable disease.

Single nucleotide polymorphisms in the GFR-related gene and the SNP-SNP interactions on the risk of diabetic kidney disease in Chinese Han population.

Genetic susceptibilityisanimportant pathogenic mechanism in diabetic kidney disease (DKD). However, the specific gene variant associatedwith DKD susceptibility remains unclear. Glomerular filtration rate (GFR), an important indicator for the process of DKD, has a heritable component. This study aimed to explore whether these GFR-related single nucleotide polymorphisms (SNPs) were associated with DKD. GFR-related SNPs were collected from the Phenotype-Genotype Integrator (PheGenI) database. SNPs for population cohort analysis were selected following the criteria of complete records of eQTL and MAF > 5% in the Chinese Han population. Totally 498 subjects participated, including166 patients with DKD, 166 patients with T2DM, and 166 controls. The genotypes of SNPs were determined using a Sequenom MassARRAY system. Plink software was employed to analyze the SNP-SNP interactions. By screening the GFR-related SNPs recorded in the PheGenI database, four SNPs (rs1260326, rs17319721, rs35716097, and rs6420094) werefinally selected to investigate the association with DKD. It was shown that one of the four SNPs was related to DKD. The G allele of SLC34A1 rs6420094 was associated with a decreased risk of DKD in DKD and T2DM groups (OR 0.716; P = 0.049). Genetic model analysis revealed that rs6420094 was a protective factor for DKD in T2DM in a dominant model and an additive model (P = 0.03; P = 0.032, respectively). Although rs17319721 was not associated with the risk of DKD, the SNP-SNP interactions between rs17319721 and rs6420094 predicted a significantly decreased risk of DKD (OR 0.464; P = 0.047). SLC34A1 rs6420094 was associated with a decreased DKD risk in the Chinese Han population. SNP-SNP interaction between rs17319721 and rs6420094 was associated with a lower risk of DKD.

Genetic analysis by targeted next-generation sequencing and novel variation identification of maple syrup urine disease in Chinese Han population

Maple syrup urine disease (MSUD) is a rare autosomal recessive disorder that affects the degradation of branched chain amino acids (BCAAs). Only a few cases of MSUD have been documented in Mainland China. In this report, 8 patients (4 females and 4 males) with MSUD from 8 unrelated Chinese Han families were diagnosed at the age of 6 days to 4 months. All the coding regions and exon/intron boundaries of BCKDHA, BCDKHB, DBT and DLD genes were analyzed by targeted NGS in the 8 MSUD pedigrees. Targeted NGS revealed 2 pedigrees with MSUD Ia, 5 pedigrees with Ib, 1 pedigree with MSUD II. Totally, 13 variants were detected, including 2 variants (p.Ala216Val and p.Gly281Arg) in BCKDHA gene, 10 variants (p.Gly95Ala, p.Ser171Pro, p.Phe175Leu, p.Arg183Trp, p.Lys222Thr, p.Arg285Ter, p.Arg111Ter, p.S184Pfs*46, p.Arg170Cys, p.I160Ffs*25) in BCKDHB gene, 1 variant (p.Arg431Ter) in DBT gene. In addition, 4 previously unidentified variants (p.Gly281Arg in BCKDHA gene, p.Ser171Pro, p.Gly95Ala and p.Lys222Thr in BCKDHB gene) were identified. NGS plus Sanger sequencing detection is effective and accurate for gene diagnosis. Computational structural modeling indicated that these novel variations probably affect structural stability and considered as likely pathogenic variants.

Sirtuin3 rs28365927 functional variant confers to the high risk of non-alcoholic fatty liver disease in Chinese Han population

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a multifactorial condition associated with aging, insulin resistance, metabolic syndrome, genetic factors and more. Although genetic traits are among the most important risks factors for NAFLD, the understanding of their influence is still quite limited. The present study aimed at identifying novel single nucleotide polymorphisms (SNPs) that may confer a risk for NAFLD in the Han Chinese population.MethodsBased on the “two-hit hypothesis”, candidate SNPs, including Sirtuin3 rs28365927, were genotyped by MassARRAY in B-type ultrasonography-proven NAFLD patients (n = 292) and healthy controls (n = 387).ResultsIn a model analysis of individuals matched based on gender and age that compared 223 NAFLD and 223 non-NAFLD patients, the rs28365927 GA + AA genotype was a significant risk factor for the development of NAFLD in a dominant model. Rs28365927 was significantly associated with a higher NAFLD risk in both an additive model (A vs G) and genotypic model (GA vs GG). Among the NAFLD patients, serum levels of total bilirubin (TBIL), DBIL direct bilirubin (DBIL) and glutamic-pyruvic transaminase (ALT) in rs28365927 A allele carriers (GA + AA) were 11.1, 14.7 and 41.5% higher, respectively, than in non-carriers (GG). Furthermore, among the NAFLD patients, the carriers of Rs28365927 allele A were positively correlated with higher ALT levels.ConclusionSirtuin3 rs28365927 functional variant confers to the high risk of non-alcoholic fatty liver disease in Chinese Han population. The rs28365927 A allele significantly increased the ALT levels of NAFLD patients.

The Association between TREM2 Gene and Late-Onset Alzheimer’s Disease in Chinese Han Population

Objective: : The objective of this study was to evaluate the impact of single nucleotide polymorphisms (SNPs) in triggering receptor expressed on the myeloid cells 2 protein (TREM2) gene and their interaction with environmental factors and haplotypes on late-onset Alzheimer’s disease (LOAD). Methods: DNA was extracted from the whole blood of the participants and genotyped using PCR and followed by restriction fragment length polymorphism. The Hardy-Weinberg equilibrium test was used in the control group. Multivariate logistic regression analysis was used to determine the relationship between the 4 SNPs of the TREM2 gene and the risk of LOAD. Generalized multifactor dimensionality reduction was used to test the best interaction combination between SNPs and environmental factors. Results: Logistic regression analysis showed that the T allele of rs75932628 and the T allele of rs2234253 were independently associated with increased risk of LOAD, and adjusted odds ratios (ORs) were 1.81 (1.271–2.35) and 1.59 (1.15–2.03), respectively. However, there was no significant association with LOAD for rs142232675 and rs143332484. We found a best model significantly associated with LOAD risk that consisted of rs75932628 and smoking, which scored 10/10 for both the sign test and cross-validation consistency (p = 0.012). Stratified analysis indicated that current smokers with rs75932628-CT/TT genotype have the highest LOAD risk compared to never smokers with rs75932628 – CC genotype, OR (95% confidence interval) = 2.73 (1.72–3.79). Haplotypes of rs75932628 and rs2234253 were analyzed using the SHEsis online software. However, no haplotype was found to be significantly associated with the risk of LOAD. Conclusions: The T allele of rs75932628 and the T allele of rs2234253 and interaction between rs75932628 and smoking were all correlated with increased risk of LOAD.

"Linkage and Association Between Several Variants in the Apo CIII Gene Regions and risk of Coronary Artery Disease in Chinese Han Population"

Coronary Artery Disease (CAD) remains a significant health concern worldwide. Dyslipidemia has been identified as one of the principal risk factors for the development of CAD...

Association and interaction effect of UCP2 gene polymorphisms and dietary factors with congenital heart diseases in Chinese Han population

Congenital heart diseases (CHDs) are the most common birth defects and the leading cause of non-infectious deaths in infants, with an unknown etiology. We aimed to assess the association of genetic variations in UCP2 gene, dietary factors, and their interactions with the risk of CHDs in offspring. The hospital-based case–control study included 464 mothers of children with CHDs and 504 mothers of healthy children. The exposures of interest were maternal dietary factors in early pregnancy and UCP2 genetic variants. Logistic regression analyses were used to assess the association and interaction of UCP2 gene and dietary factors with CHDs. Our results found that the polymorphisms of UCP2 gene at rs659366 and rs660339, together with maternal dietary factors including excessive intake of pickled vegetables and smoked foods were associated with increased risks of CHDs in offspring. Regular intake of fresh meat, fish and shrimp, and milk products were associated with lower risks of CHDs in offspring. Besides, positive interaction between the dominant model of rs659366 and excessive intake of pickled vegetables was found in the additive interaction model (RERI = 1.19, P = 0.044). These findings provide the theoretical basis for gene screening and a new clue for the prevention of CHDs in offspring.

A 3′ Untranslated Region Polymorphism of CTNNB1 (Rs2953) Alters MiR-3161 Binding and Affects the Risk of Ischemic Stroke and Coronary Artery Disease in Chinese Han Population

Background: CTNNB1 is reported to be related to the pathological process of ischemic stroke (IS) and coronary artery disease (CAD). Polymorphism located in the 3′ untranslated region (3′UTR) of a gene might affect gene expression by modifying binding sites for microRNAs (miRNAs). This study aimed to analyze the association between polymorphism rs2953, which locates in the 3′UTR of CTNNB1, and the risk of IS and CAD. Methods: The CTNNB1 messenger RNA (mRNA) expression level in peripheral venous blood was measured. In total, 533 patients with IS, 500 patients with CAD, and 531 healthy individuals were genotyped by Sequenom Mass­Array technology. The binding of miR-3161 to CTNNB1 was determined by dual-luciferase reporter assay. Results: The CTNNB1 mRNA expression level for the IS group was significantly lower than that for the control group. Rs2953 was significantly associated with both IS risk and CAD risk. Significant association was also found between polymorphism rs2953 and many conventional factors, such as serum lipid level, blood coagulation markers, blood glucose level, and homocysteine level in patients. Rs2953 T allele introduced a binding site to miRNA-3161 and thus decreased luciferase activity. Conclusion: Polymorphism rs2953 is associated with the risk of both IS and CAD. Moreover, polymorphism rs2953 (T) introduces a binding site to miRNA-3161 and thus decreases luciferase activity in cell lines.

Association of ADAM10 gene variants with sporadic Parkinson's disease in Chinese Han population.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Genetic factors play important roles in PD risk. rs653765 and rs514049 of ADAM10 were reported to be associated with Alzheimer's disease (AD) in Caucasian population; however, the association of the two variants with PD in Chinese Han population remains unknown. The present investigation aimed to explore the possible association of ADAM10 variants with PD in Chinese Han population. We enrolled 565 PD patients and 518 healthy controls to conduct a case-control study. DNA samples were extracted from peripheral blood leukocytes, and the genotypes were determined by utilization of MassARRAY platform. Plasma levels were measured by enzyme-linked immunosorbent assay (ELISA). We found CC genotype of rs514049 was associated with an increased risk of PD (OR (95% CI) = 3.776 (1.127-11.217), p = 0.018). The C allele frequency of rs514049 was significantly higher in PD group (OR (95% CI) = 1.328 (1.031-1.709), p = 0.028), especially in male subgroup (OR (95% CI) = 1.484 (1.053-2.092), p = 0.024). However, there was no significant difference in the genotype or allele frequencies for rs653765 within the groups. Plasma levels were significantly decreased in PD patients compared with controls (p < 0.001). Our data suggested that C allele of rs514049 in ADAM10 may increase the risk of PD in Chinese Han population, especially in males. The decreased plasma levels are probably involved in PD development.

Association study of genetic variants at TTC32-WDR35 gene cluster with coronary artery disease in Chinese Han population.

BackgroundTTC32‐WDR35 gene cluster has been genome‐wide significantly associated with coronary artery disease (CAD). However, the common variants in this region contributing to CAD risk remain elusive.MethodsWe performed a case‐control study enrolling 935 CAD cases and 935 age‐sex‐frequency‐matched controls from unrelated southwest Chinese Han population. Five variants were determined by TaqMan assay.ResultsThis study indicated that rs721932 CG genotype was associated with CAD risk (OR = 0.68, 95% CI: 0.54‐0.86; P = .001). Stratified analysis showed that the risk associated with rs12617744 AA genotype was robust in male (OR = 0.62, 95% CI: 0.42‐0.93, P = .02). The gene dosage of the risk allele at rs12617744 showed a significant association with left circumflex artery disease (P = .027) and the number of vascular lesions in patients (P = .034). Moreover, the gene dosage of rs721932 risk allele was associated with vascular lesion numbers (P = .048) and the progression of CAD (P = .028). Compared with carriers of major alleles, the AA genotype of rs12617744 and GG genotype of rs721932 were both associated with plasma HDL level (P = .009 and 0.004, respectively). Expression quantitative trait locus (eQTL) results showed significantly different TTC32 expression of subjects as a function of SNPs (rs2278528, rs7594214, and rs721932) genotype in the artery. Besides, FPRP analysis did support the strong links between polymorphisms and CAD risk.ConclusionsSNP rs721932 at TTC32‐WDR35 Gene Cluster was associated with CAD risk, and rs12617744 was associated with the risk of CAD among males. Both SNPs may contribute to the regulation of plasma HDL levels and possibly to the severity of CAD in Chinese Han population.

Association of ADAM10 gene variants with sporadic Parkinson's disease in Chinese Han population

Objective: Parkinson's disease (PD) is the second-most common neurodegenerative disease in the world. Genetic factors play important role in familial and sporadic PD. Recently, rs653765 and rs514049 of ADAM10 gene variants were reported to be associated with Alzheimer disease (AD) in Caucasian population. However, the role of these variants in the pathogenesis of PD is unknown. Hence, to investigate the association between ADAM10 variants (rs653765 and rs514049) and PD susceptibility, we conducted a case-control study.

Plasma P-selectin level is associated with severity of coronary heart disease in Chinese Han population.

ObjectiveThis study aimed to evaluate the association between plasma P-selectin levels and the severity of coronary heart disease (CHD) in a Chinese Han population.MethodsWe enrolled 219 patients with CHD and 168 healthy individuals without CHD as a control group. Coronary stenosis was evaluated based on the number of diseased coronary arteries and the Gensini scoring system. P-selectin levels were quantified by enzyme-linked immunosorbent assay and the association between CHD and plasma P-selectin level was analyzed.ResultsP-selectin levels were significantly higher in CHD patients compared with controls. Levels were highest in patients with three-vessel disease and lowest in those with one-vessel disease, with significant differences among the groups. P-selectin levels were also highest in the high-score and lowest in the low-score group according to Gensini score, with significant differences among the groups. P-selectin level was significantly positively correlated with Gensini score and C-reactive protein level. Elevated P-selectin was identified as an independent risk factor for CHD.ConclusionP-selectin levels were increased in Chinese Han patients with CHD. P-selectin level is an independent risk factor for CHD and may serve as a biomarker reflecting the severity of CHD in the Chinese Han population.

Common variation of the NSD1 gene is associated with susceptibility to Hirschsprung's disease in Chinese Han population.

Hirschsprung's disease (HSCR) is the most common congenital cause of intestinal obstruction in children. Sotos syndrome (SoS) is an overgrowth disorder with constipation and sometimes accompanied by HSCR. NSD1 gene mutation is the main cause of SoS. We aimed to investigate association of NSD1 common single nucleotide polymorphisms (SNPs) with HSCR susceptibility in Chinese Han population. We genotyped 15 SNPs encompassing NSD1 gene region in 420 HSCR patients and 1665 controls on Fludigm EP1 platform. Association analysis was performed between cases and controls. Rs244709 was the most associated SNP with HSCR susceptibility of the sample set (PAllelic = 9.69 × 10-5, OR = 1.37, 95% CI: 1.17-1.61). Gender stratification analysis revealed that NSD1 SNPs were associated with HSCR in males, but not in females. The nonsynonymous coding SNP rs28932178 in NSD1 exon 5 represented the most significant signal in males (PAllelic = 6.43 × 10-5, OR = 1.42, 95% CI: 1.20-1.69). The associated SNPs were expression quantitative trait loci (eQTLs) of nearby genes in multiple tissues. NSD1 expression levels were higher in aganglionic colon tissues than ganglionic tissues (P = 3.00 × 10-6). NSD1 variation conferred risk to HSCR in males, indicating SoS and HSCR may share common genetic factors. This is the first study to reveal that NSD1 variation conferred risk to Hirschsprung's disease susceptibility in males of Chinese Han population, indicating Sotos syndrome and Hirschsprung's disease may share some common genetic background. This study indicates more attention should be paid to the symptom of constipation in patients with Sotos syndrome. Our results raise questions about the role of NSD1 in the development of enteric nervous system and the pathogenesis of Hirschsprung's disease.

The association between TLR3 rs3775290 polymorphism and sporadic Parkinson’s disease in Chinese Han population

Accumulating evidences have pointed out that neuroinflammation is involved in Parkinson’s disease (PD) pathogenesis. Toll-like receptor 3 (TLR3), as a member of pattern-recognition receptors (PRRs), is known to play a pivotal role in inflammatory responses and immune responses. It was recently suggested that TLR3 was increased in the animal models of PD. The present study aimed to evaluate whether TLR3 gene (rs3775290) polymorphism was associated with PD susceptibility. We genotyped the single-nucleotide polymorphism (SNP) of TLR3 gene (rs3775290) using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) from 380 PD patients and 380 control subjects in Chinese Han population. Our data demonstrated that rs3775290 T allele carriers were associated with a reduced risk of PD between early-onset PD(EOPD)group and its healthy-matched control subgroup (OR = 0.571, 95 %CI = 0.366–0.891, P = 0.013 for TT + TC vs CC). Moreover, there were significant differences in genotype and allele distribution between EOPD group and the late-onset PD (LOPD) group (P = 0.024 and P = 0.008, respectively). Therefore, our study suggested a possible association between TLR3 (rs3775290) gene polymorphism and PD susceptibility, indicating that T allele of rs3775290 might be a protective factor for sporadic PD in Han Chinese population.

Association of GLP-1 receptor gene polymorphisms with sporadic Parkinson’s disease in Chinese Han population

The Glucagon Like Peptide 1 Receptor (GLP1R) plays a critical role in selective death of dopaminergic neurons and development of Parkinson’s disease (PD). However, little is known about genetic associations of GLP1R gene polymorphisms with PD susceptibility. Therefore, this study aimed to verify whether GLP1R polymorphisms contribute to PD risk in a Chinese Han population. We recruited 518 individuals comprising 259 sporadic PD patients and 259 healthy controls. All of the participants were genotyped for two possibly functional polymorphisms located in GLP1R (rs3765467 and rs6923761) using the Sequenom MassARRAY platform. The frequency of the rs3765467 GG genotype was significantly higher in the PD group compared with that in the control group (OR = 1.444, 95 % CI: 1.015–2.055, p = 0.041). Subgroup analysis revealed that male patients and late-onset patients with the rs3765467 GG genotype suffered an increased risk of PD compared with healthy controls (p = 0.021 and p = 0.012, respectively). However, the genotype and allele frequencies for rs6923761 were not significantly different between PD and healthy subjects. Our results indicate that the GLP1R rs3765467 GG genotype is a potential risk factor for PD, especially for male and late-onset PD patients in the Chinese Han population.

Association analysis of 15 GWAS-linked loci with Parkinson’s disease in Chinese Han population

Genetic factors play an important role in Parkinson’s disease (PD) and vary from different races. A previous genome-wide association study (GWAS) identified 17 novel risk loci that were associated with PD in Caucasians. Several subsequent studies investigated the association between these loci and PD in Chinese populations. However, the results on the role of these variants for PD have been conflicting. To explore the relationship of 15 controversial loci with PD in the Chinese Han population, we performed a case-control study including 492 PD patients and 524 healthy controls. iMLDR technology was used to type 15 GWAS-linked loci of 1016 blood samples from all subjects. We found that rs34043159 (IL1R2) (dominant model after adjusted: p = 0.011, OR 95 % CI 0.577 (0.378–0.880)) and rs4073221 (SATB1) (allele model: p = 0.001, OR 95 % CI 0.542 (0.371–0.792); dominant model after adjusted: p = 0.049, OR 95 % CI 0.587 (0.345–0.998)) were associated with PD. After age onset and gender subgroup analysis, rs34043159 (IL1R2) (χ2 = 7.971, p = 0.019) and rs4073221 (SATB1) (χ2 = 12.673, p = 0.001) were associated with late-onset PD. rs34043159 (IL1R2) was associated with PD in females (χ2 = 7.227, p = 0.027) rather than males (χ2 = 1.100, p = 0.577). rs4073221 (SATB1) was associated with PD in both males (χ2 = 10.270, p = 0.005) and females (χ2 = 7.050, p = 0.022). Further studies are needed to explore the role of IL1R2 and SATB1 in the pathogenesis of PD.

Contribution of IL-7/7R genetic polymorphisms in coronary heart disease in Chinese Han population

BackgroundCoronary heart disease (CHD) is a common chronic inflammatory disease. Interleukin (IL)-7/IL-7R has been reported to be involved in the development of CHD. However, the relationship between IL-7/7R genetic polymorphisms and CHD among the Han Chinese population remains unclear. MethodsTo examine whether IL-7/7R variants contributed to CHD, six single-nucleotide polymorphisms (SNPs) were genotyped by using the Agena MassARRAY platform in 499 CHD patients and 496 controls. Logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). The linkage disequilibrium was analyzed using Haploview software. The association between clinical parameters and IL-7/7R polymorphisms was determined by a one-way ANOVA. ResultsIL-7R rs969129 G (OR = 1.20, 95% CI: 1.00–1.43, p = 0.047) allele and GG (OR = 1.45, 95% CI: 1.01–2.08, p = 0.044) genotype carriers had a higher risk for CHD. IL-7R haplotype “ACAG” (OR = 1.43, 95% CI: 1.09–1.87, p = 0.010) conferred an increased CHD risk. Rs969129, rs6451231, and rs117173992 were related to CHD susceptibility in males and/or the subgroup of individuals aged >61 years. IL-7R rs969129, rs10053847, rs6451231, and rs118137916 variants were associated with diabetes in patients with CHD. Moreover, rs969129, rs6451231, and rs117173992 were associated with high-density lipoprotein cholesterol (HDL-C) concentrations, whereas rs118137916 and rs10053847 were associated with low-density lipoprotein cholesterol (LDL-C) levels (p < 0.05). ConclusionIL-7/7R variants were related to the genetic predisposition of CHD in the Chinese Han population. These findings increase our knowledge regarding the effect of IL-7/7R on CHD.

Fine mapping of thyroglobulin gene identifies two independent risk loci for Graves' disease in Chinese Han population.

This study aimed to determine independent risk loci of Graves' disease (GD) in the thyroglobulin (TG) region. In this two-staged association study, a total of 9,757 patients with GD and 10,626 sex-matched controls were recruited from Chinese Han population. Illumina Human660-Quad BeadChips in the discovery stage and TaqMan SNP Genotyping Assays in the replication stage were used for genotyping. Trend test and logistic regression analysis were performed in this association study. In the discovery stage, rs2294025 and rs7005834 were the most highly associated susceptibility loci with GD in TG. In the replication phase, 7 SNPs, including rs2294025 and rs7005834, were selected for fine-mapping. Finally, we confirmed that rs2294025 and rs7005834 were the independent risk loci of GD in the combined populations. At the same time, there was no significant difference between the risk allele frequencies of rs2294025 and rs7005834 in different clinical phenotypes of GD. The fine mapping study of thyroglobulin identified two independent SNPs (rs2294025 and rs7005834) for GD susceptibility. However, no significant differences for rs2294025 and rs7005834 were observed, between the different clinical phenotypes of GD, including gender, Graves' ophthalmopathy (GO), and serum levels of thyrotropin receptor antibody, thyroid peroxidase antibody, and thyroglobulin antibody. These results provide a deeper understanding of the association mechanism of thyroglobulin and GD risk.

Association Between Single Nucleotide Polymorphisms in the Vitamin D Receptor and Incidence of Dry Eye Disease in Chinese Han Population

BackgroundDry eye disease (DED) is a chronic dysfunction of the ocular surface and has become an important public problem. Vitamin D receptor (VDR) gene polymorphism has been found to be associated with different kinds of diseases. The relationship between single nucleotide polymorphisms (SNPs) in the VDR gene should be studied.Material/MethodsIn the present case-control study, we investigated the association of VDR gene polymorphism with DED risk. Clinical data including age, gender, body mass index (BMI, kg/m2), smoking history, diabetes, and blood pressure were recorded. Serum 25-hydroxy vitamin D (25[OH]D) was chosen as the main parameter that reflected the level of vitamin D. We identified SNPs of VDR gene Apa-1, Bsm-1, Fok-1, and Taq-1 in both DED cases and healthy controls.ResultsA total of 124 DED cases and 135 healthy controls were included in this study. It was reported that aa in Apa-1 (OR=2.803, 95% CI, 1.350–5.820) and tt in Taq-1 (OR=0.362, 95% CI, 0.141–0.930) were associated with increased the risk of DED. Analysis of the allele frequencies of VDR gene polymorphisms among DED patients and healthy controls showed that allele differences in Apa-1 were significantly associated with higher risk.ConclusionsSNPs of VDR gene (Apa-1 and Taq-1) were associated with the risk of DED. No significant association of Bsm-1 and Fok-1 in VDR gene demonstrated significant effect in the incidence of DED. Thus, we found that several SNPs of VDR gene could provide significant pathogenic effects in the risk of DED.