Association of CDKN2A/CDKN2B Gene Polymorphisms with Increased Susceptibility to Intracranial Aneurysm in a Chinese Han Population.
Ontology highlight
ABSTRACT: Objective
Several studies have reported that single-nucleotide polymorphisms (SNPs) of the CDKN2A/CDKN2B gene on chromosome 9p21.3 are associated with increased risk of intracranial aneurysm (IA). However, the association between IAs and SNPs of CDKN2A/CDKN2B in Chinese Han people is yet to be evaluated. This study examined the association of the SNPs rs10811661 and rs4977574 with IA in the Chinese Han population.Methods
A total of 595 IA patients and 600 sex- and age-matched controls were enrolled in the study. Peripheral blood was collected and stored at -80°C until use. CDKN2A/CDKN2B was identified using polymerase chain reaction-ligase detection reaction. SNP genotyping was performed for rs10811661 and rs4977574 using a MassArray system. Associations between these two SNPs and IAs was tested with χ2 or Fisher's exact tests and multivariate logistic regression.Results
rs10811661 and rs4977574 were significantly associated with IA. The frequency of rs10811661-T in IA was higher than in controls (OR 1.26, 95% CI 1.07-1.49; P<0.01). There was no significant difference in frequency of haplotype between control subjects and IA patients.Conclusion
rs10811661 and rs4977574 on 9p21.3 were strongly associated with genetic susceptibility to IA in the Chinese Han population, which emphasizes a need for further investigation.
SUBMITTER: Cui X
PROVIDER: S-EPMC8126964 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:PurposeIntracranial aneurysms (IA) comprise a multifactorial disease with unclear physiological mechanisms. The lysyl oxidase (LOX) family genes (LOX, LOX-like 1-4) plays important roles in extracellular matrix (ECM) reconstruction and has been investigated in terms of susceptibility to IA in a few populations. We aimed to determine whether polymorphisms in LOX family genes are associated with susceptibility to IA in a Chinese population.MethodsThis case-control study included 384 patients with IA and 384 healthy individuals without IA (controls). We genotyped 27 single nucleotide polymorphisms (SNPs) of LOX family genes using the Sequenom MassARRAY® platform. These SNPs were adjusted for known risk factors and then, odds ratios (OR) and 95% confidence intervals (CI) were evaluated using binary logistic regression analysis.ResultsThe result showed that LOX rs10519694 was associated with the risk of IA in recessive (OR, 3.88; 95% CI, 1.12-13.47) and additive (OR, 1.56; 95%CI, 1.05-2.34) models. Stratified analyses illustrated that LOX rs10519694 was associated with the risk of single IA in the recessive (OR, 3.95; 95%CI, 1.04-15.11) and additive (OR, 1.64; 95%CI, 1.04-2.56) models. The LOXL2 rs1010156 polymorphism was associated with multiple IA in the dominant model (OR, 1.92; 95%CI, 1.02-3.62). No associations were observed between SNPs of LOXL1, LOXL3, and LOXL4 and risk of IA.ConclusionLOX and LOXL2 polymorphisms were associated with risk of single IA and multiple IA in a Chinese population, suggesting potential roles of these genes in IA. The effects of these genes on IA require further investigation.
| S-EPMC8355735 | biostudies-literature
Project description:CDKN2BAS gene polymorphisms has been shown to correlation with intracranial aneurysm(IA) in the study of foreign people. The study, the author selected the Chinese people as the research object to explore whether CDKN2BAS gene polymorphisms associated with Chinese patients with IA.We selected 200 patients(52.69?±?11.50) with sporadic IA as experimental group, 200 participants(49.99?±?13.00) over the same period to the hospital without cerebrovascular diseases as control group. Extraction of peripheral blood DNA, applying polymerase chain reaction(PCR)-ligase detection reaction (LDR) identified CDKN2BAS Single nucleotide polymorphism(SNP) locus genotype: rs6475606, rs1333040, rs10757272, rs3217992, rs974336, rs3217986, rs1063192. The differences in allelic and genotype frequencies between the patient and control groups were evaluated by the chi-square test or Fisher's exact tests.The genotype of rs1333040 and rs6475606 shown association with sporadic IA(X2?=?8.545, P?=?0.014; X2?=?10.961, P?=?0.004; respectively);the C allele of rs6475606 showed reduction the occurrence of IA; the rs1333040 and rs6475606 associated with hemorrhage, the C allele of rs1333040 could lower the risk of hemorrhage, and rs6475606 will not, rs1333040 also associated with aneurysm size.Our research shows that variant rs1333040 and rs6475606 of CDKN2BAS related to the Chinese han population of sporadic IAs occurs. This study confirms the association between CDKN2BAS and IAs.
| S-EPMC5725912 | biostudies-literature
Project description:Purpose Colorectal cancer (CRC) is among the most common cancers worldwide and an important cause of cancer-related death. Inherited genetic variation plays a vital role in the occurrence and development of CRC. The aim of this study was to evaluate the association of single nucleotide polymorphisms (SNPs) in MMP2 with CRC risk. Patients and Methods Three candidates, MMP2 SNPs, rs1053605, rs243849, and rs14070, were selected and genotyped using the Agena MassARRAY RS1000 system, and their association with risk of CRC was evaluated in 663 CRC cases and 663 healthy controls by calculating odds ratio (OR) with 95% confidence interval (95% CI) values. Results The minor allele of rs243849 (T) was significantly less frequent in cases than controls (p = 0.021), and this SNP was associated with a decreased risk of CRC under co-dominant (p = 0.033), dominant (p = 0.021), and log-additive (p = 0.017) models, after adjusting for confounding factors. After stratification, rs243849 was found to be protective against CRC in patients who were non-smoking, consumed alcohol, and were ≥60 years old (p < 0.05). Conversely, rs1053605 was associated with disease occurrence in patients with CRC who consumed alcohol and were <60 years old (p < 0.05). Furthermore, rs1053605 genotype was associated with an increased risk of colon cancer (p < 0.05), while that of rs243849 was associated with a decreased risk of rectal cancer (p < 0.05). The rs1053605-rs243849 CT haplotype exhibited a protective role in CRC risk, following adjustment for confounders (p = 0.014). The rs14070 SNP was not associated with CRC risk. Finally, the false discovery rate (FDR) method was used to validate the study results. Conclusion Overall, the MMP2 gene polymorphisms, rs243849 and rs1053605, may be useful for predicting CRC progression.
| S-EPMC9270925 | biostudies-literature
Project description:Intracranial aneurysm (IA) is a complex disease caused by genetic and environmental factors. Evidence indicates that inflammation plays an important role in IA occurrence. We aimed to explore the associations between inflammatory cytokine gene polymorphisms and IA in a Chinese population. This study enrolled 768 participants of Han ethnicity, including 384 patients with IA and 384 healthy individuals. Sixteen single nucleotide polymorphisms (SNPs) of IL1, IL6, IL12, and TNF-α genes were genotyped using the Sequenom MassARRAY platform. Univariate and multivariate logistic regression analyses were used to analyze the associations. We found IL12B rs3181216 was significantly associated with IA in the recessive and additive models (OR = 0.46, 95% CI = 0.23-0.89, P = 0.022; OR = 0.74, 95% CI = 0.56-0.98, P = 0.034, respectively). TNF-α rs1799964 was associated with IA in dominant and additive models (OR = 0.67, 95% CI = 0.46-0.98, P = 0.041; OR = 0.71, 95% CI = 0.51-0.98, P = 0.034, respectively). IL1A rs17561 was associated with single IA susceptibility (dominant model: OR = 0.52, 95% CI = 0.31-0.85, P = 0.040). The IL12B rs3181216 polymorphism was associated with single IA susceptibility in the recessive model (OR = 0.41, 95% CI = 0.18-0.93, P = 0.033). The IL12B rs2195940 polymorphism was associated with multiple IAs susceptibility (dominant model: OR = 0.28, 95% CI = 0.09-0.89, P = 0.031; additive model: OR = 0.28, 95% CI = 0.09-0.90, P = 0.032). TNF-α rs1799964 was associated with multiple IAs susceptibility in the dominant model (OR = 0.54, 95% CI = 0.30-0.97, P = 0.040). No associations were found between other polymorphisms and IA susceptibility. Therefore, IL1A, IL12B, and TNF-α gene polymorphisms are associated with IA susceptibility in a Chinese population.
| S-EPMC7826207 | biostudies-literature
Project description:PurposeGenetic factors play a vital role in intracranial aneurysm (IA) onset and development. Studying the relationship between IA and the Sox17 polymorphisms in diverse populations is essential for establishing credibility.Patients and methodsWe collected blood samples derived from a total of 596 sporadic IA patients and 600 individual controls in several medical institutes in China. We used the Sequenom MassArray system for single nucleotide polymorphisms (SNPs) genotyping after DNA extraction. The SNPs data was tested and analyzed in PLINK (version 1.9). Multiple-testing was performed in PLINK to make the statistics more rigorous and accurate.ResultsWe found that the allelic G of rs1072737 (OR=1.303, genomic-control corrected P-value =0.001032) is a risk allele, while the allelic G of rs9298506 (OR=0.7253, genomic-control corrected P-value =0.01559) is a protective allele in Chinese Han people.ConclusionThe allelic G of rs1072737 is a risk factor for IA, while the allelic G of rs9298506 serves as a protective factor for IA in Chinese Han people.
| S-EPMC6452799 | biostudies-literature
Project description:To investigate the association of three polymorphisms in the receptor for advanced glycation end product (RAGE) gene with Crohn's disease (CD) risk in a Chinese population.A hospital-based case-control association study involving 312 CD patients and 479 healthy controls was conducted. Peripheral blood samples were collected from 791 study subjects, and genomic DNA was extracted. Genotyping was performed using polymerase chain reaction-ligase detection reaction method. The association between polymorphic genotype and CD predisposition was determined using odds ratio and 95% confidence interval (CI). Data were analyzed using Haplo.stats program.Significant differences were observed between patients and controls in allele/genotype distributions of rs1800624 (P(allele)=0.012; P(genotype)=0.005) and in allele distributions of rs2070600 (P=0.02). The risk for CD associated with the rs1800624-A mutant allele decreased by 36% (95%CI: 0.47-0.88, P = 0.005) under the additive model and by 35% (95%CI: 0.46-0.91, P=0.013) under the dominant model. Carriers of rs2070600-A mutant allele showed a 37% (95%CI: 1.02-1.83, P=0.036) increased risk of developing CD relative to the GG genotype carriers. In haplotype analysis, haplotype T-A-G (in the order rs1800625, rs1800624, and rs2070600) decreased the odds of CD by 33% (95%CI: 0.49-0.94, P=0.018).CD is an immune-related disease with genetic predisposition. Genetic defects in the RAGE gene are strongly associated with CD in Chinese population.
| S-EPMC3942844 | biostudies-literature
Project description:Recently, MDM4 gene has been reported to be a susceptibility gene for glioma in Europeans, but the molecular mechanism of glioma pathogenesis remains unknown. The aim of this study was to investigate whether common variants of MDM4 contribute to the risk of glioma in Han Chinese individuals. A total of 24 single-nucleotide polymorphisms (SNPs) of the MDM4 gene were assessed in a dataset of 562 glioma patients (non-glioblastoma) and 1,192 cancer-free controls. The SNP rs4252707 was found to be strongly associated with the risk of non-GBM (P?=?0.000101, adjusted odds ratio (OR)?=?1.34, 95% confidence interval (CI)?=?1.16-1.55). Further analyses indicated that there was a significant association between A allele of rs4252707 associated with the increased non-GBM risk. Haplotype analysis also confirmed a result similar to that of the single-SNP analysis. Using stratification analyses, we found the association of rs4252707 with an increased non-GBM risk in adults (?18 years, P?=?0.0016) and individuals without IR exposure history (P?=?0.0013). Our results provide strong evidence that the MDM4 gene is tightly linked to genetic susceptibility for non-GBM risk in Han Chinese population, indicating a important role for MDM4 gene in the etiology of glioma.
| S-EPMC6056491 | biostudies-literature
Project description:PurposeLRRC3B gene, as a tumor suppressor gene was involved in the development and progress of breast cancer (BC). However, the effect of LRRC3B polymorphisms on BC has rarely been reported. In the study, we aimed to evaluate the relation between LRRC3B variants and BC risk.MethodsAmong 563 BC patients and 552 healthy controls, ten single-nucleotide polymorphisms (SNPs) in LRRC3B were genotyped by Agena MassARRAY. Odds ratios (ORs) and 95% confidence interval (CI) were calculated using logistic regression model.ResultsOur study demonstrated that rs1907168 polymorphism (heterozygous: OR = 0.71, p = 0.017) was related to the reduced risk of BC in the overall. In stratified analyses by age, rs1907168 was associated with the decreased (heterozygous: OR = 0.53, p = 0.002) while rs78205284 (homozygote: OR = 2.83, p = 0.034) increased BC susceptibility among the population at age ≤51 years. Rs6551122 (recessive: OR = 0.51, p = 0.028) and rs12635768 (homozygote, OR = 0.36, p = 0.023) polymorphisms were related to the smaller BC tumor size (<2 cm). In addition, rs112276562 (heterozygote OR = 0.56, p = 0.002), rs6551122 (heterozygote OR = 0.63, p = 0.016), and rs73150416 (heterozygote OR = 0.57, p = 0.005) variants contributed to the lower incidence of PR-positive BC. Moreover, rs6788033 was associated with a lower expression level of Ki-67 (log-additive: OR = 0.68, p = 0.024). Furthermore, we found an association of 'GATT' haplotype with an increased risk for BC. In addition, LRRC3B gene was down-regulated in BC tumor and had a poor prognosis in BC in in silico analysis.ConclusionOur study firstly found LRRC3B SNPs contributed to the risk of BC, suggesting LRRC3B variants might help to predict BC progression.
| S-EPMC8222685 | biostudies-literature
Project description:Psoriasis is a common disease in dermatology, but its etiology and pathogenesis have not been fully elucidated. In recent years, researchers have found that HOX transcript antisense RNA (HOTAIR) plays an important role in biological processes as an important long-chain noncoding RNA (lncRNA). The goal of this study was to investigate the association between HOTAIR polymorphisms and psoriasis in a Chinese Han population by screening key candidate single-nucleotide polymorphism (SNPs) sites in HOTAIR. A total of 269 patients diagnosed with psoriasis and 273 healthy control subjects were enrolled in this case-control study. Three SNPs of HOTAIR were genotyped: SNP1 (rs12826786), SNP2 (rs1899663), and SNP3 (rs4759314). All polymorphisms were in Hardy-Weinberg equilibrium in both the control and patient groups, and the SNPs were in linkage disequilibrium. The distribution of the rs4759314 genotype in the control group and case group was statistically significant according to all the models except the recessive model (adjusted p value < 0.05), and the CCG haplotype group had a significant difference (OR (95%CI) = 2.907 (1.344 - 6.289), adjusted p value = 0.0263). rs12826786 was associated with a risk of psoriasis according to the dominant model (C/T-T/T vs. C/C: OR (95%CI) = 0.70 (0.48 - 1.01), adjusted p value = 0.049) and overdominant model (C/T vs. C/C-T/T: OR (95%CI) = 0.69 (0.47 - 1.01), adjusted p value = 0.048). The current work showed that a genomic variant within HOTAIR was associated with a risk of psoriasis, and the clinical value of this study should be further evaluated in the future.
| S-EPMC8357505 | biostudies-literature
Project description:OBJECTIVE:Worldwide, the highest frequencies of APOL1-associated kidney variants are found in indigenous West Africans among whom small vessel disease (SVD) ischemic stroke is the most common stroke phenotype. The objective of this study was to investigate the association and effect sizes of 23 selected SNPs in 14 genes of relevance, including the APOL1 G1 variants, with the occurrence of SVD ischemic stroke among indigenous West African participants in the Stroke Investigative Research and Education Network (SIREN) Study. MATERIALS AND METHODS:Cases were consecutively recruited consenting adults (aged 18 years or older) with neuroimaging-confirmed first clinical stroke. Stroke-free controls were ascertained using a locally validated version of the Questionnaire for Verifying Stroke-Free Status (QVSFS). Logistic regression models adjusting for known vascular risk factors were fitted to assess the associations of the 23 SNPs in rigorously phenotyped cases (N = 154) of SVD ischemic stroke and stroke-free (N = 483) controls. RESULTS:Apolipoprotein L1 (APOL1) rs73885319 (OR = 1.52; CI: 1.09-2.13, P-value = .013), rs2383207 in CDKN2A/CDKN2B (OR = 3.08; CI: 1.15-8.26, P -value = .026) and rs2107595 (OR = 1.70; CI: 1.12-2.60, P-value = .014) and rs28688791 (OR = 1.52; CI: 1.03-2.26, P-value = .036) in HDAC9 gene were associated with SVD stroke at 0.05 significance level. Polymorphisms in other genes did not show significant associations. CONCLUSION:This is the first report of a specific association of APOL1 with a stroke subtype. Further research is needed to confirm these initial findings and deepen understanding of the genetics of stroke in people of African ancestry with possible implications for other ancestries as all humans originated from Africa.
| S-EPMC5716854 | biostudies-literature