Association of lipid metabolism relevant gene FBXW7 polymorphism with coronary artery disease in Uygur Chinese population in Xinjiang, China: a case-control.
ABSTRACT: BACKGROUND:Hyperlipidemia is a major risk factor for coronary artery disease (CAD). As F-box and WD repeat domain-containing 7 (FBXW7) gene is an important regulating factor for lipid metabolism, the aim of the present study is to assess the association between human FBXW7 gene polymorphisms and CAD among Han Chinese and Uygur Chinese populations in Xinjiang, China. METHODS:A total of 1,312 Han Chinese (650 CAD patients and 662 controls) and 834 Uygur Chinese (414 CAD patients and 420 controls) were enrolled in this case-control study. Three single nucleotide polymorphisms (SNPs) rs2255137 T>C, rs2292743 A>T, rs35311955 G>C of FBXW7 were selected and genotyped using the improved multiplex ligase detection reaction (iMLDR) method. RESULTS:We found that the rs2255137 CC genotype was very common in the CAD patients compared with the control subjects in the Uygur Chinese populations. After adjustments for several confounders: age, gender, smoking, drinking, hypertension, diabetes, TG, TC, HDL-C and LDL-C, this association remained significant. Furthermore, we investigated the relationships between rs2255137 genotypes and the circulating serum lipid levels and found that people carrying the C allele of rs2255137 may have higher serum lipid levels in the Uygur Chinese populations. CONCLUSION:Our results indicate that rs2255137 in FBXW7 gene is associated with CAD in the Uygur Chinese population in China.
Project description:Hyperlipidemia is a major risk factor for coronary artery disease (CAD). The current study was designed to explore the possible correlation between single nucleotide polymorphisms (SNPs) in the lipid homeostasis regulatory genes F-box and WD repeat domain-containing 7 (FBXW7) and sterol regulatory element-binding proteins (SREBPs) with CAD among Han Chinese and Uygur Chinese populations in Xinjiang, China.In the Uygur Chinese population, rs9902941 in SREBP-1 and rs10033601 in FBXW7 were found to be associated with CAD in a recessive model (TT vs. CT + CC, P = 0.032; GG vs. AG + AA, P = 0.010, respectively), and rs7288536 in SREBP-2 was found to be associated with CAD in an additive model (CT vs. CC + TT, P = 0.045). The difference was statistically significant in the Uygur Chinese population after multivariate adjustments [Odds ratio (OR) = 1.803, 95% confidence interval (CI): 1.036~3.137, P = 0.037; OR = 1.628, 95% CI: 1.080~2.454, P = 0.020; OR = 1.368; and 95% CI: 1.018~1.837, P = 0.037, respectively]. There were also significant interactions between the above-mentioned models in the Uygur Chinese population. However, these relationships were not observed before or after multivariate adjustment in the Han Chinese population.A total of 1,312 Han Chinese (650 CAD patients and 662 controls) and 834 Uygur Chinese (414 CAD patients and 420 controls) were enrolled in this case-control study. Three SNPs (rs9902941 in SREBP-1, rs7288536 in SREBP-2 and rs10033601 in FBXW7) were selected and genotyped using the improved multiplex ligase detection reaction (iMLDR) method.The results of this study indicate that variations in the lipid regulatory pathway genes FBXW7 and SREBPs (rs9902941 in SREBP-1, rs7288536 in SREBP-2 and rs10033601 in FBXW7) are associated with CAD in the Uygur Chinese population in Xinjiang, China.
Project description:The morbidity of coronary artery disease (CAD) in the Uygur population of Xinjiang was much higher than the national average. Clopidogrel is the most commonly used medication worldwide in dual antiplatelet therapy for CAD, and the response of clopidogrel is affected by CYP2C19, PON1, and ABCB1 genetic polymorphisms. The distribution of CYP2C19*17, ABCB1, and PON1 genetic polymorphisms in Han and Uygur populations with CAD of Xinjiang has not been investigated.This study aimed to investigate the frequencies of CYP2C19, PON1, and ABCB1 genetic polymorphisms, and to identify the metabolizer phenotype of CYP2C19 in Han and Uygur populations with CAD in Northwestern Xinjiang, China. We identified 602 Han and 527 Uygur patients from 2014 through 2019 and studied genotypes for selected allele polymorphisms using sequencing by hybridization.There were significantly different allele frequencies and genotype frequencies between the 2 ethnic groups in terms of CYP2C19*2, *3, *17, ABCB1 and PON1, (P?<?.05). For CYP2C19*17, the frequency of TT genotype was 2.5% in Uygur patients, but it was undetectable in Han patients. In both the intermediate and poor metabolizer groups, the genotypes polymorphisms CYP2C19*2, *3, *17 were significantly less common in Uygur patients than in Han patients (P?<?.001). By contrast, the proportion of ultra-metabolizers as defined by CYP2C19*2, *3, *17 polymorphisms significantly higher in Uygur patients (18.6%) than in Han patients (1.7%, P?<?.001). The CYP2C19*2 frequency was significantly different between Han patients and Han healthy groups (P?<?.001), while the CYP2C19*3 frequency was significantly different between Uygur patients and Uygur healthy groups (P?<?.001).Our study supports the notion of interethnic differences in terms of CYP2C19, PON1, and ABCB1 polymorphisms and CYP2C19 genotype-defined clopidogrel metabolic groups. These finding could provide valuable data and insights into personalized CAD treatment for the Uygur and Han populations in Xinjiang.
Project description:The relationship between CYP19A1 genetic polymorphisms and coronary artery disease (CAD) remains unclear. Thus, the aim of the present study was to investigate the association of CYP19A1 genetic polymorphisms with CAD in Han and Uygur populations and to characterize the association between the levels of sex hormones and aromatase with single-nucleotide polymorphisms (SNPs) in CYP19A1 genes in Chinese women.There were significant differences in the genotype distributions of rs2236722 and rs4646 between CAD patients and control subjects in the Uygur population. The rs4646 was found to be associated with CAD in the dominant model (CC vs. CA + AA) and the additive model (CA vs. CC + AA) (both P ? 0.001). The difference remained statistically significant after multivariate adjustment (OR = 0.483, 95% CI: 0.338-0.690, P = 0.000; and OR = 1.844, 95% CI: 1.300-2.617, P = 0.001, respectively). In normal Uygur postmenopausal women, there were significant differences in the genotype distributions of rs4646 and the circulating hormone and aromatase levels between CAD patients and control subjects. The differences in estradiol and aromatase levels remained statistically significant after multivariate adjustment (OR = 0.889, 95% CI: 0.817-0.969, P = 0.007; and OR = 0.947, 95% CI: 0.936-0.957, P = 0.000, respectively). Additionally, there were differences in sex hormone levels between the different ethnicities among the Xinjiang Chinese population.Among a total of 1,064 Han individuals (614 men and 450 women) and 790 Uygur individuals (484 men and 306 women), 498 postmenopausal women (265 Han and 233 Uygur individuals) were selected. Four SNPs (rs2236722, rs2304463, rs4646, and rs4275794) were genotyped using the improved multiplex ligation detection reaction (iMLDR) technique. The estradiol and testosterone levels were determined using a radioimmunoassay based on GC-2016?. In addition, an enzyme-linked immunosorbent assay (ELISA) was performed to determine the serum P450 aromatase levels.The results of this study indicate that the rs2236722 and rs4646 of the CYP19A1 gene are associated with CAD and circulating sex hormone levels in the Xinjiang population of China.
Project description:BACKGROUND: Endothelial cell activation and dysfunction are the foundation of atherosclerosis, including coronary artery disease (CAD). Endothelial cell activation is mediated by the level of gene transcription. Early growth response 3 (Egr3) is a critical determinant of vascular endothelial growth factor (VEGF) signalling in activated endothelial cells. If endothelial cells are excessively activated, it may lead to vasculopathic diseases, such as pathologic angiogenesis, inflammation, and atherosclerosis. The aim of the present study was to assess the association between the Egr3 gene polymorphisms and CAD. METHODS: Two independent case-control studies that involved the Han group (409 CAD patients and 351 control subjects) and the Uygur group (299 CAD patients and 303 control subjects) analysed the relationship between Egr3 SNPs (rs1996147 and rs1008949) and CAD. Genotyping was undertaken using the TaqMan SNP genotyping assay. RESULTS: The entire Uygur group and the males in the Uygur group showed a higher frequency of the A allele (rs1996147) in CAD patients than in the control subjects (P?=?0.003 and P?=?0.005, respectively). Additionally, the distribution of the recessive model of rs1996147 (AA vs GG?+?AG) for the total sample and the males was significantly different between CAD patients and control participants (P?=?0.002 and P?=?0.003, respectively), and the difference remained statistically significant following multivariate adjustment (Total: OR?=?1.705; 95% CI: 1.166-2.494, P?=?0.006; males: OR?=?1.908, 95% CI: 1.189-3.062, P?=?0.007). However, for Uygur females, we did not observe a difference in the allele frequency or genotypic distribution of rs1996147 between CAD patients and control participants. Similarly, the distribution of the rs1996147 allele frequency or genotypes showed no significant difference between patients with CAD and control participants in the Han group. The distribution of rs1008949 genotypes, dominant model, recessive model, and allele frequency did not show a significant difference between patients with CAD and the control subjects in the Han and Uygur groups. CONCLUSION: rs1996147 may be a novel polymorphism of the Egr3 gene associated with CAD in males of the Chinese Uygur population.
Project description:The nuclear factor kappa-light-chain enhancer of activated B cells (NF-?B) signaling pathway plays a key role in the regulatory network of inflammation. The deletion variant allele of the NFKB1-94 insertion/deletion (ins/del) ATTG promoter polymorphism results in lower transcription levels of the p50 subunit, and the variant allele has been associated with several inflammatory diseases as well as with coronary artery disease (CAD) with inflammation playing an important part in the pathogenesis. The aim of the present study was to assess the association between the human NFKB1 gene polymorphism and CAD in a Han and Uygur population of China.We used the following two independent case-control studies: a Han population (633 CAD patients and 616 control subjects) and a Uygur population (437 CAD patients and 356 control subjects). All participants were genotyped for the same one single nucleotide polymorphism (SNP) (rs28362491) of the NFKB1 gene, that is, DD, ATTG deleted homozygote; ID, ATTG inserted and deleted heterozygote and II, ATTG inserted homozygote by real-time polymerase chain reaction.The distribution of the SNP (rs28362491) genotypes was significantly different between CAD and control participants in women of the Han (p=0.029) and the Uygur (p=0.032) populations, but not in men. Further, DD carriers of the SNP in the NFKB1 gene were more frequent in female CAD patients than in controls in both the Han (23.2% vs. 13.5%, p=0.009) and the Uygur (19.8% vs. 8.3%, p=0.012) population. The significant difference between DD and ID+II genotypes was retained after adjustment for covariates (for Han, odds ratio [OR]: 1.805, p=0.029 and for Uygur, OR: 3.192, p=0.011).The DD genotype of the SNP (rs28362491) in the NFKB1 gene may be considered a genetic marker of CAD in Han and Uygur women in China.
Project description:BACKGROUND:Schizophrenia is a severe mental disease with high morbidity and heritability. The SLC39A8 gene is located in 4q24 and encodes a protein that transports many metal ions. Multiple previous studies found that one of the most pleiotropic single nucleotide polymorphisms (SNPs) in SLC39A8, rs13107325, is associated with schizophrenia in the European population. However, the polymorphism of this locus is rare in other populations. In China, the Han Chinese and the Uygur Chinese are two ethnic populations that originate from different races. METHODS:A case-control study was conducted with 983 schizophrenia cases and 1230 healthy controls of the Chinese Uygur population. To validate the most promising SNP, meta-analyses were conducted with the Han Chinese and the European PGC2 data sets reported previously. RESULTS:A susceptible locus, rs10014145 (pallele?=?0.014, pallele?=?0.098 after correction; pgenotype?=?0.004, pgenotype?=?0.032 after correction) was identified in case-control study of the Chinese Uygur population. Further, the association between rs10014145 and schizophrenia was supported by a meta-analysis of Han and Uygur Chinese samples (pooled OR [95% CI] =1.10 [1.03-1.17], Z?=?2.73, p?=?0.006). The association between rs10014145 and schizophrenia was not significant in a meta-analysis of combined Chinese and European samples (pooled OR [95% CI] =1.07 [1.00-1.14], Z?=?1.88, and p?=?0.06). In addition, the "CCAC" haplotype of rs4698844-rs233814-rs13114343-rs151394 was significantly associated with schizophrenia in Uygur Chinese (P?=?0.003, corrected p?=?0.012). CONCLUSIONS:The results of this study support that SLC39A8 is a susceptible gene for schizophrenia in the populations of Han Chinese and Uygur Chinese in China, further studies are suggested to validate the association.
Project description:The cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) gene is expressed in the vascular endothelium, which metabolizes arachidonic acid into 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs). 20-HETE mediates cardiovascular homeostasis and growth response in vascular smooth muscle cells (VSMCs) as well as the anti-platelet effect. EETs are potent endogenous vasodilators and inhibitors of vascular inflammation. This study assessed the association between human CYP1A1 gene polymorphisms and coronary artery disease (CAD) in the Uygur and Han in China.Two independent case-control studies that recruited Han (389 patients with CAD and 411 controls) and Uygur participants (293 patients with CAD and 408 controls) analyzed the relationship between CYP1A1 single nucleotide polymorphisms (SNPs: rs4886605, rs12441817, rs4646422 and rs1048943) and CAD. All patients with CAD and controls were genotyped for the four SNPs of CYP1A1 using TaqMan SNP genotyping assays.In the Uygur group, the distribution of the dominant model(CC vs CT?+?TT) of rs4886605 for the total sample and the males was significantly different between CAD patients and control participants (P?=?0.001 and P?=?0.012, respectively), The difference remained significant after a multivariate adjustment (P?=?0.018, P?=?0.015, respectively). The rs12441817 was also associated with CAD in a dominant model for all participants (P?=?0.003) and men (P?=?0.012), and the difference remained significant after a multivariate adjustment (P?=?0.016, P?=?0.002, respectively). However, we did not observe differences in the Uygur females and Han group with regard to the allele frequency or genotypic distribution of rs4886605 and rs12441817 between patients with CAD and control participants. Patients with CAD did not significantly differ from the control participants with regard to the distributions of rs4646422 and rs1048943 genotypes, the dominant model, the recessive model, or allele frequency in the Han and Uygur groups.Both rs4886605 and rs12441817 SNPs of the CYP1A1 gene are associated with CAD in the Uygur population of China.
Project description:Polymorphisms in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene are associated with severe hypercholesterolemia and stroke. Here, we investigated the relationship between single nucleotide polymorphisms in PCSK9 and stroke in 237 patients with lacunar infarction in the Uygur and Han populations in Xinjiang Uygur Autonomous Region of China. Using the SNaPshot single-base terminal extension method, four PCSK9 gene polymorphisms were analyzed. We found a significantly strong relationship between the PCSK9 rs17111503 (G > A) polymorphism and increased susceptibility to lacunar infarction by variant homozygote comparison, and using the dominant and recessive models in the Han population but not in the Uygur population. Low triglyceride levels were found in AA carriers (rs17111503, G > A) in the Han population but not in the Uygur population. Association analysis revealed that the rs17111503 (G > A) polymorphism was not significantly associated with smoking, alcohol drinking, history of hypertension or diabetes in the Han or Uygur lacunar infarction patients. rs11583680, rs483462 and rs505151 were not associated with risk of lacunar infarction in the Han or Uygur populations. Our findings suggest that the PCSK9 rs17111503 (G > A) polymorphism is associated with susceptibility to lacunar infarction in the Han population but not in the Uygur population.
Project description:BACKGROUND:The present study aimed to investigate the genetic polymorphisms in exon 4 of the NOD2 gene in tuberculosis patients and healthy controls, in order to clarify whether polymorphisms in the NOD2 gene is associated with tuberculosis. METHODS:A case-control study was performed on the Chinese Han, Uygur and Kazak populations. Exon 4 of the NOD2 gene was sequenced in 425 TB patients and 380 healthy controls to identify SNPs. RESULTS:The frequency of T/G genotypes for the Arg587Arg (CGT → CGG) single nucleotide polymorphism (SNP) in NOD2 was found to be significantly higher in the Uygur (34.9%) and Kazak (37.1%) populations than the Han population (18.6%). Also, the frequency of G/G genotypes for the Arg587Arg SNP was significantly higher in the Uyghur (8.3%) and Kazak (5.4%) populations than the Han population (0.9%). Meanwhile, no significant difference was found in the Arg587Arg polymorphism between the tuberculosis patients and healthy controls in the Uyghur and Kazak populations (P > 0.05) whereas, a significant difference was observed in the Arg587Arg polymorphism between the tuberculosis patients and healthy controls in the Han population (P < 0.01). The odd ratio of 2.16 (95% CI = 1.31-3.58; P < 0.01) indicated that the Arg587Arg SNP in NOD2 may be associated with susceptibility to tuberculosis in the Chinese Han population. CONCLUSIONS:Our study is the first to demonstrate that the Arg587Arg SNP in NOD2 is a new possible risk factor for tuberculosis in the Chinese Han population, but not in the Uyghur and Kazak populations. Our results may reflect racial differences in genetic susceptibility to tuberculosis.
Project description:The secretive Klotho protein is an anti-aging regulatory hormone that plays a physiological role in many target organs. The present study aims to investigate the correlation between Klotho gene and mild cognitive impairment (MCI) in Uygur and Han populations in Xinjiang. From July 2008 to April 2014, stratified random multistage cluster sampling was used in combination with the methods of on-site questionnaire and household survey to conduct a cross-sectional MCI investigation on selected Uygur and Han subjects aged over 60 years old in Xinjiang region. 323 Uygur and Han MCI patients were randomly selected and matched with 343 subjects in the normal control group. SNaPshot technique was used to detect the polymorphisms of Klotho gene. A case-control associated analysis was conducted to analyze the genotype and allele frequencies of single nucleotide polymorphisms (SNPs) in the MCI group and the normal control group. The polymorphisms of rs1207568 and rs9536314/rs9527025 loci in Klotho gene were different among MCI populations in Xinjiang, and after group assignments based on ethnic background, the polymorphisms of rs1207568 and rs9536314/rs9527025 loci were associated with the Uygur MCI population and were not relevant to the Han MIC population. The frequencies of mutational alleles of rs9536314/rs9527025 locus in the Uygur population were significantly higher than those in the Han population. The genotype and allele frequencies of rs1207568 locus in the Uygur and Han populations were similar. The polymorphisms of rs1207568 and rs9536314/rs9527025 loci in Klotho gene may be associated with the Uygur MCI population in Xinjiang.