NFKB1 gene rs28362491 ins/del variation is associated with higher susceptibility to myocardial infarction in a Chinese Han population.
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ABSTRACT:
SUBMITTER: Luo JY
PROVIDER: S-EPMC7658993 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
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Project description:The acute coronary syndrome (ACS) is a complex disease where genetic and environmental factors are involved. NF-κB, a central regulator of inflammation, is involved in various inflammatory diseases. The aim of the present study was to explore the association between NFKB1 gene rs28362491 (-94ATTGins/del) polymorphism and ACS. A total of 778 ACS patients and 1112 healthy subjects were included in our study. The TaqMan SNP genotyping assays was used to analyze the rs28362491 polymorphism. The lesion extent of coronary artery was assessed by Gensini Score and lesion vessel number in ACS patients. For total and males, the frequencies of the mutant DD genotype and D allele were significantly higher in ACS patients than that in control subjects (total: DD genotype: 18.0 vs 14.1%, P=0.009, D allele: 43.0 vs 37.9%, P=0.002, males: DD genotype: 20.6 vs 15.3%, P=0.042, D allele: 44.2 vs 38.8%, P=0.013). After multivariate logistic regression analysis, we found that individuals with mutant DD genotype had 1.329-fold higher risk of ACS compared with individuals with ID and II genotypes. Moreover, ACS patients with DD genotype were worse stenosis of coronary artery compared with patients carrying II or ID genotype. In conclusion, our study demonstrated that the mutant DD genotype of NFKB1 gene was associated with the risk and severity of ACS in Han population in Xinjiang, northwest of China.
| S-EPMC6470809 | biostudies-literature
Project description:Inflammation is a risk factor for coronary heart disease (CHD). A common deletion-allele in the promoter region of NFKB1 results in lower protein levels of the NF-?B p50 subunit. Recent evidence suggests that the NF-?B p50 dimer has anti-inflammatory effects. We aimed to investigate the association of the functional ATTG NFKB1 insertion/deletion variant with risk of CHD in three independent prospective studies of generally healthy men and women.The NFKB1 ins/del polymorphism was genotyped in studies of CHD nested within the Diet, Cancer and Health (DCH) study, the Health Professionals Follow-up (HPFS) and the Nurses' Health (NHS) studies, totaling 1008, 428 and 439 cases, respectively. The minor allele frequency in the combined sample was 0.38 among controls. In a pooled analysis, the relative risk (RR) among heterozygous men and women was 1.22 (95% CI: 1.07-1.40), compared to the most common ins/ins genotype. The RR among homozygotes was 1.20 (95% CI: 0.94-1.53). There was no evidence of an allele-dosage effect, and in a dominant model the RR among del-allele carriers was 1.22 (95% CI: 1.07-1.39). The risk was similar in women and men (RR was 1.20 in women and 1.23 in men, respectively). The NFKB1 variant was not associated with plasma lipid levels, but del-carriers had lower levels of C-reactive protein.The NFKB1 promoter variant, previously shown to cause partial depletion of NF-?B p50, was associated with a higher risk of CHD in three independent prospective studies of generally healthy Caucasians.
| S-EPMC3827022 | biostudies-literature
Project description:Coronary artery disease (CAD) is considered as a chronic inflammatory disease initiated from early childhood. Nuclear factor ?B (NF ?B) and ?B1A (NF ?B1A) are the key regulators of inflammatory responses. The NFKB1 -94ATTG ins/del and NFKB1A -826C/T polymorphisms may contribute to the development of CAD. The aim of the present study was to investigate the association of these polymorphisms with the risk of CAD. The study population included 120 patients with angiographically confirmed CAD and 100 matched controls. Genotyping of NFKB1 -94ATTG ins/del and NFKB1A -826C/T polymorphism was performed using PCR-RFLP method. Lipid level was determined by routine colorimetric methods. Statistical analysis was done by SPSS 16 software. Results indicated that the genotypic (P=0.041) and allelic (P=0.009) distribution of the NFKB1-94ATTG ins/del polymorphism was significantly different between the two groups. In the univariate analysis (ins/ins genotype as reference), the del/del genotype (OR=2.88, 95% CI=1.21-6.84, P=0.015) but not ins/del genotype (OR=1.48, 95% CI=0.83-2.64, P=0.191) was significantly associated with the increased risk of CAD. In the multiple binary logistic regression analysis, diabetes, hypertension, smoking, LDL-cholesterol, total cholesterol, HDL-cholesterol and NFKB1 -94ATTG del/del genotype were identified as significant and independent risk factors for CAD development. The distribution of genotypes and alleles of NFKB1A -826C/T polymorphism was not significantly different between the two groups. In conclusion the present study identified NFKB1 -94ATTG ins/del polymorphism but not NFKB1A -826C/T polymorphism as a significant and independent risk factor for development and severity of CAD.
| S-EPMC5991530 | biostudies-literature
Project description:AIM:To investigate the association of NFKB1 gene -94 ATTG insertion/deletion (rs28362491) polymorphism with inflammatory markers and risk of diabetic nephropathy in Asian Indians. METHODS:A total of 300 subjects were recruited (100 each), normoglycemic, (NG); type 2 diabetes mellitus (T2DM) without any complications (DM) and T2DM with diabetic nephropathy [DM-chronic renal disease (CRD)]. Analysis was carried out by polymerase chain reaction-restriction fragment length polymorphism and ELISA. Pearson's correlation, analysis of variance and logistic regression were used for statistical analysis. RESULTS:The allelic frequencies of -94 ATTG insertion/deletion were 0.655/0.345 (NG), 0.62/0.38 (DM) and 0.775/0.225 (DM-CRD). The -94 ATTG ins allele was associated with significantly increased levels of urinary monocyte chemoattractant protein-1 (uMCP-1); uMCP-1 (P = 0.026) and plasma tumor necrosis factor-alpha (TNF-?); TNF-? (P = 0.030) and almost doubled the risk of diabetic nephropathy (OR = 1.91, 95%CI: 1.080-3.386, P = 0.025). CONCLUSION:-94 ATTG ins/ins polymorphism might be associated with increased risk of developing nephropathy in Asian Indian subjects with diabetes mellitus.
| S-EPMC5320420 | biostudies-literature
Project description:BackgroundA functional -94 insertion/deletion polymorphism (rs28362491) in the promoter of the NFKB1 gene was reported to influence NFKB1 expression and confer susceptibility to different types of cancer. This study aims to determine whether the polymorphism is associated with risk of bladder cancer.Materials and methodsTaqMan assay was used to determine genotype among 609 cases and 640 controls in a Chinese population. Logistic regression was used to assess the association between the polymorphism and bladder cancer risk, and quantitative real-time polymerase chain reaction was used to determine NFKB1 mRNA expression.ResultsCompared with the ins/ins/ins/del genotypes, the del/del genotype was associated with a significantly increased risk of bladder cancer [adjusted odd ratio (OR) = 1.92, 95% confidence interval (CI) = 1.42-2.59]. The increased risk was more prominent among subjects over 65 years old (OR = 2.37, 95% CI= 1.52-3.70), male subjects (OR = 1.97, 95% CI = 1.40-2.79) and subjects with self-reported family history of cancer (OR = 3.59, 95% CI = 1.19-10.9). Furthermore, the polymorphism was associated with a higher risk of developing non-muscle invasive bladder cancer (OR= 2.07, 95% CI= 1.51-2.85), grade 1 bladder cancer (OR = 2.40, 95% CI = 1.68-3.43), single tumor bladder cancer (OR = 2.04, 95% CI = 1.48-2.82) and smaller tumor size bladder cancer (OR = 2.10, 95% CI= 1.51-2.92). The expression of NFKB1 mRNA in bladder cancer tissues with homozygous insertion genotype was higher than that with deletion allele.ConclusionsIn conclusion, the -94 ins/del ATTG polymorphism in NFKB1 promoter may contribute to the etiology of bladder cancer in the Chinese population.
| S-EPMC3748046 | biostudies-literature
Project description:Nuclear factor- κ B is associated with the pathogenesis of numerous malignancies, and the functional polymorphism -94ins/del ATTG (rs28362491) in the human NFKB1 gene is associated with cancer risk. Previous studies on the association between the -94ins/del ATTG polymorphism and cancer risk reported conflicting results. To clarify this relationship, we performed a meta-analysis of 21 case-control studies involving 6127 cases and 9238 controls. We used pooled odds ratios (ORs) with their 95% confidence intervals (95% CIs) to assess the association. We found that the NFKB1 promoter -94ins/del ATTG polymorphism was significantly associated with cancer risk in four genetic models (ins/ins versus del/del, OR = 1.47, 95% CI = 1.11-1.93; dominant model, OR = 1.26, 95% CI = 1.03-1.53; recessive model, OR = 1.26, 95% CI = 1.05-1.51; ins allele versus del allele, OR = 1.19, 95% CI = 1.05-1.35). Stratified analyses revealed a significant association between the polymorphism and ovarian, oral, and prostate cancers. Similar results were determined in an Asian population and not in a Caucasian population. Thus, our results suggested that the polymorphism can contribute to cancer risk. Moreover, the polymorphism can exert race- and cancer-specific effects on cancer risk. Further large-scale and functional studies are necessary to elucidate this possible effect.
| S-EPMC4033547 | biostudies-literature
Project description:Background A functional -94 insertion/deletion polymorphism (rs28362491) in the promoter of the NFKB1 gene was reported to influence NFKB1 expression and confer susceptibility to different types of cancer. This study aims to determine whether the polymorphism is associated with risk of bladder cancer. Materials and methods TaqMan assay was used to determine genotype among 609 cases and 640 controls in a Chinese population. Logistic regression was used to assess the association between the polymorphism and bladder cancer risk, and quantitative real-time polymerase chain reaction was used to determine NFKB1 mRNA expression. Results Compared with the ins/ins/ins/del genotypes, the del/del genotype was associated with a significantly increased risk of bladder cancer [adjusted odd ratio (OR) =1.92, 95% confidence interval (CI), 1.42-2.59]. The increased risk was more prominent among subjects over 65 years old (OR =2.37, 95% CI, 1.52-3.70), male subjects (OR =1.97, 95% CI, 1.40-2.79) and subjects with self-reported family history of cancer (OR =3.59, 95% CI, 1.19-10.9). Furthermore, the polymorphism was associated with a higher risk of developing non-muscle invasive bladder cancer (OR =2.07, 95% CI, 1.51-2.85), grade1 bladder cancer (OR =2.40, 95% CI, 1.68-3.43), single tumor bladder cancer (OR =2.04, 95% CI =1.48-2.82) and smaller tumor size bladder cancer (OR =2.10, 95% CI, 1.51-2.92). The expression of NFKB1 mRNA in bladder cancer tissues with homozygous insertion genotype was higher than that with deletion allele. Conclusions In conclusion, the -94 ins/del ATTG polymorphism in NFKB1 promoter may contribute to the etiology of bladder cancer in the Chinese population.
| S-EPMC4708321 | biostudies-literature
Project description:SIRT1 exerts protective effects against endothelial cells dysfunction, inflammation and atherosclerosis, indicating an important role on myocardial infarction (MI) pathogenesis. Nonetheless, the effects of SIRT1 variants on MI risk remain poorly understood. Here we aimed to investigate the influence of SIRT1 polymorphisms on individual susceptibility to MI. Genotyping of three tagSNPs (rs7069102, rs3818292 and rs4746720) in SIRT1 gene was performed in a Chinese Han population, consisting of 287 MI cases and 654 control subjects. In a logistic regression analysis, we found that G allele of rs7069102 had increased MI risk with odds ratio (OR) of 1.57 [95% confidence interval (CI) = 1.15-2.16, Bonferroni corrected P (Pc) = 0.015] after adjustment for conventional risk factors compared to C allele. Similarly, the combined CG/GG genotypes was associated with the increased MI risk (OR = 1.64, 95% CI = 1.14-2.35, Pc = 0.021) compared to the CC genotype. Further stratified analysis revealed a more significant association with MI risk among younger subjects (? 55 years old). Consistent with these results, the haplotype rs7069102G-rs3818292A-rs4746720T containing the rs7069102 G allele was also associated with the increased MI risk (OR = 1.41, 95% CI = 1.09-1.84, Pc = 0.040). However, we did not detect any association of rs3818292 and rs4746720 with MI risk. Our study provides the first evidence that the tagSNP rs7069102 and haplotype rs7069102G-rs3818292A-rs4746720T in SIRT1 gene confer susceptibility to MI in the Chinese Han population.
| S-EPMC4338141 | biostudies-literature
Project description:This study aimed to clarify the influence of a common insertion/deletion polymorphism (-94ins/del ATTG, rs28362491) in the Nuclear factor-?B1 (NFKB1) promoter on non-small cell lung cancer (NSCLC) susceptibility. We genotyped the NFKB1 -94ins/del ATTG polymorphism by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and assessed the association with NSCLC risk, clinicopathological parameters in a case-control study of 421 cases and 425 controls. Heterozygous (ID) genotype disclosed a statistically significantly increased risk of developing NSCLC (OR = 1.57, 95% CI 1.13-2.19, P = 0.007). Homozygous (II) genotype also showed an increased risk of NSCLC (OR = 1.87, 95% CI 1.27-2.75, P = 0.001). Statistically significant difference was observed when the patients and controls were compared according to ID + II versus DD (OR = 2.01, 95% CI 1.47-2.76, P<0.001). The I allele was significantly higher in the NSCLC cases compared to the controls (52.9% versus 45.1%). The I allele was significantly associated with NSCLC risk (OR = 1.37, 95% CI 1.12-1.65, P = 0.001). There was a significantly higher frequency of ID + II genotypes observed in smokers, compared to non-smokers (OR = 1.99, 95% CI 1.22-3.24, P = 0.005) and in patients with stage III + IV, compared to stage I + II (OR = 2.16, 95% CI 1.34-3.49, P = 0.002). This study suggested that NFKB1 -94ins/del ATTG polymorphism was significantly associated with NSCLC risk in Chinese Han population.
| S-EPMC4509329 | biostudies-literature
Project description:Numerous studies have implicated the Wnt pathway in the development and progression of myocardial infarction (MI); however, there are very few investigations addressing the effects of polymorphisms in the Wnt pathway genes on MI susceptibility. We investigated the possible correlation between genetic variations in Wnt pathway genes and MI risk. Three polymorphisms (rs7832767 C > T in SFRP1 gene, rs2293303 C > T in CTNNB1 gene, rs16893344 C > T in WISP1 gene) were finally selected and genotyped in 465 MI patients and 485 healthy controls, using the PCR-RFLP method. We found that the SFRP1 rs7832767 variant allele (T) was associated with a significantly increased risk of MI [TT vs. CC: adjusted odds ratio (AOR) = 3.13, 95% CI = 1.78-5.51; CT/TT vs. CC: AOR = 1.53, 95% CI = 1.12-2.08; TT vs. CC/CT:AOR = 2.87, 95% CI = 1.66-4.97)]. The significant association with MI risk was also found for the CTNNB1 rs2293303 (CT vs. CC: AOR = 3.48, 95% CI = 2.28-5.33; TT vs. CC: AOR = 7.37, 95% CI = 2.08-26.16; CT/TT vs. CC: AOR = 3.72, 95% CI = 2.46-5.62; TT vs. CC/CT:AOR = 5.52, 95% CI = 1.58-19.28), and WISP1 rs16893344 polymorphisms (CT vs. CC: AOR = 2.43, 95% CI = 1.70-3.47; TT vs. CC: AOR = 5.17, 95% CI = 1.85-14.41; CT/TT vs. CC: AOR = 2.58, 95% CI = 1.83-3.66; TT vs. CC/CT:AOR = 3.88, 95% CI = 1.41-10.64). The associations remain significant in stratified analysis by demographic and clinical characteristics of participants, with few exceptions. Our study provided the first evidence of the association between polymorphisms in the Wnt pathway genes and MI susceptibility in Chinese Han population. Epidemiological studies with larger samples and functional analyses are warranted to further verify our results.
| S-EPMC5288145 | biostudies-literature