Genetic Variation in NFKB1 and NFKBIA and Susceptibility to Coronary Artery Disease in a Chinese Uygur Population

et al. 2016

Hum Genomics

BackgroundChronic inflammation has been widely considered to be the major risk factor of coronary heart disease (CHD). The goal of our study was to explore the possible association with CHD for inflammation-related single nucleotide polymorphisms (SNPs) involved in cytosine-phosphate-guanine (CpG) dinucleotides. A total of 784 CHD patients and 739 non-CHD controls were recruited from Zhejiang Province, China. Using the Sequenom MassARRAY platform, we measured the genotypes of six inflammation-related CpG-SNPs, including IL1B rs16944, IL1R2 rs2071008, PLA2G7 rs9395208, FAM5C rs12732361, CD40 rs1800686, and CD36 rs2065666). Allele and genotype frequencies were compared between CHD and non-CHD individuals using the CLUMP22 software with 10,000 Monte Carlo simulations.ResultsAllelic tests showed that PLA2G7 rs9395208 and CD40 rs1800686 were significantly associated with CHD. Moreover, IL1B rs16944, PLA2G7 rs9395208, and CD40 rs1800686 were shown to be associated with CHD under the dominant model. Further gender-based subgroup tests showed that one SNP (CD40 rs1800686) and two SNPs (FAM5C rs12732361 and CD36 rs2065666) were associated with CHD in females and males, respectively. And the age-based subgroup tests indicated that PLA2G7 rs9395208, IL1B rs16944, and CD40 rs1800686 were associated with CHD among individuals younger than 55, younger than 65, and over 65, respectively.ConclusionsIn conclusion, all the six inflammation-related CpG-SNPs (rs16944, rs2071008, rs12732361, rs2065666, rs9395208, and rs1800686) were associated with CHD in the combined or subgroup tests, suggesting an important role of inflammation in the risk of CHD.

Section: Resultsmentioning

confidence: 99%

Association of six CpG-SNPs in the inflammation-related genes with coronary heart disease

et al. 2016

Hum Genomics

“…All participants were selected from the Cardiovascular Risk Survey (CRS) study, aged from 35 to 88 years and recruited between 2007 and 2010. Full details of the CRS study have been published elsewhere [ 16 ]. The study was approved by the Ethics Committee of the First Affiliated Hospital of Xinjiang Medical University and was conducted in accordance with the standards of the Declaration of Helsinki (Ethics Approval Number:20080724).…”

Section: Methodsmentioning

confidence: 99%

Appropriate LDL-C-to-HDL-C Ratio Cutoffs for Categorization of Cardiovascular Disease Risk Factors among Uygur Adults in Xinjiang, China

Lai

et al. 2016

IJERPH

Self Cite

Elevated LDL-C/HDL-C ratio has been shown to be a marker of lipid metabolism as well as a good predictor of coronary artery disease (CAD). Thus, the aim of this study was to investigate whether the LDL-C/HDL-C ratio is useful for detecting cardiovascular disease (CVD) risk factors in general healthy Uygur adults in Xinjiang. A total of 4047 Uygur subjects aged ě35 years were selected from the Cardiovascular Risk Survey (CRS) study which was carried out from October 2007 to March 2010. Anthropometric data, blood pressure, lipid profile and fasting glucose were measured in all participants. The prevalence, sensitivity, specificity and distance on the receiver operating characteristic (ROC) curve of each LDL-C/HDL-C ratio were calculated. The prevalence of high LDL-C and low HDL-C cholesterol was high and positively correlated with higher LDL-C/HDL-C ratio in the Uygur population. In both men and women, we detected a slight apparent trend of high prevalence of hypertension and hypercholesterolemia with higher LDL-C/HDL-C ratio. Our study also demonstrated that the discriminatory power of the LDL-C/HDL-C ratio for CVD risk factors was slightly stronger in men than in women. Analysis of the shortest distance in the ROC curves for hypertension, dyslipidemia, diabetes, or ětwo of these risk factors suggested a LDL-C/HDL-C ratio cutoff of 2.5 for both men and women. The results of this study showed that a LDL-C/HDL-C ratio cut-off of 2.5 might be used as the predictive marker to detect CVD risk factors among Uygur adults in Xinjiang.

“…This result was consistent with our previous studies. Our previous studies reported that this variation was correlated with CAD in Chinese Han and Uygur populations 15,36 . Therefore, together with these above-mentioned studies, these findings clearly indicated the NFKB1 gene rs28362491 variation was more likely to be an independent risk factor for susceptibility of MI.…”

Section: Discussionmentioning

confidence: 81%

“…NFKB1 gene rs28362491 encodes p50/p105 submits of NF-κB family and locates at chromosome 4q24. A four base ATTG insertion/deletion (ins/del) variation located in −94 loci of NFKB1 promoter has been reported, which encodes three genotypes: wild-type homozygous insertion (II genotype), variant homozygous deletion (DD genotype) and heterozygous (ID genotype) 15 . Studies have shown that individuals who carried NFKB1 gene rs28362491 D allele or DD genotype were more susceptible to inflammatory diseases such as inflammatory bowel disease 16 , ulcerative colitis 17,18 and atherosclerotic cardiovascular diseases including coronary artery disease (CAD) [19][20][21] in different populations.…”

mentioning

confidence: 99%

NFKB1 gene rs28362491 ins/del variation is associated with higher susceptibility to myocardial infarction in a Chinese Han population

Luo

Fang

et al. 2020

Sci Rep

Self Cite

Myocardial infarction (MI), the leading cause of mortality and disability worldwide, is a disease in which multiple environmental and genetic factors are involved. Recently, researches suggested that insertion/deletion (ins/del) variation of NFKB1 gene rs28362491 is a functional polymorphism. In the present study, we aimed to explore the relation between variation of NFKB1 gene rs28362491 and MI by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) in 359 MI patients and 1085 control participants. Gensini score was used to evaluate the degree of coronary artery stenosis in MI patients. The plasma levels of interleukin-6 (IL-6), IL-8, malonaldehyde (MDA) and superoxide dismutase (SOD) were randomly measured by ELISA both in MI patients and control participants. We found that the detected frequencies of D allele (41.2% vs. 36.4%, P = 0.021) and DD genotype (17.5% vs. 12.0%, P = 0.022) were significantly higher in MI patients than in control participants. Compared with II or ID genotype carriers, the Gensini score in MI patients with DD genotype was 32–43% higher (both P < 0.001). Moreover, DD genotype carries had more diseased coronary arteries (P = 0.001 vs. II or ID genotype). Of note, IL-6 levels in MI patients carrying DD genotype were significantly higher than that in control participants and other genotype carriers in MI patients (both P < 0.05). In conclusion, NFKB1 gene rs28362491 DD genotype was associated with a higher risk of MI and more severe coronary artery lesion, which also had a potential influence on the level of inflammatory cytokine IL-6.