| Objective:(1) A systematic review and meta-analysis was conducted to investigate whether there is robust association between an insertion/deletion polymorphic variation in the NFKB1 promoter region(NFKB1-94ins/del ATTG, rs28362491) and the risk for coronary artery disease(CAD).(2) To explore the association of genetic polymorphisms in NFKBIA and NFKB1 gene and coronary coronary artery disease susceptibility in the Uygur?Han and Hazark population of Xinjiang.(3) To investigate the impact of NFKB1 polymorphism on plasma levels of IL-6 in a Chinese Uygur population. Methods:(1) Pub Med, Embase, Cochrane Library and CNKI database were searched up to 30 July 2015. All observational studies that investigated the association of NFKB1-94ins/del ATTG polymorphism and CAD risk were enrolled. Two reviewers independently selected the studies and extracted the data.(2) We genotyped NFKB1-94ins/del ATTG(rs28362491) and NFKBIA promoter polymorphisms(-881A/G,-826C/T, and-297C/T) using Taq Man SNP genotyping assays in Xinjiang Uygur, Han, Hazark CAD cases and CAD-negtive controls. The linkage disequilibrium was also performed and the haplotype was built. For those genotypes and haplotypes with significant difference between two groups entered into non-conditional logistic regression model to assess the risk associated with each SNP and major risk factors.(3) IL-6 plasma levels were measured in 360 stable CAD(SCAD) cases and 360 controls using ELISA method. Results:(1) Overall, comparison with I allele and II homozygote, D allele, ID heterozygote and DD homozygote had 13%(OR=1.13, 95%CI 1.06–1.19, P<0.001), 11%(OR=1.11, 95%CI 1.01–1.21, P=0.025), and 26%(OR=1.26, 95%CI 1.12–1.43, P<0.001) increased risk for CAD respectively. Subgroup analysis by ethnicity indicated that DD homozygotes were associated with a 47% increased risk for CAD in Asian population(OR=1.47, 95%CI 1.21–1.78, P<0.001), while ID genotype and additive model were associated with a 14%(OR=1.14, 95%CI 1.02-1.28, P=0.018) and 21%(OR=1.21, 95%CI 1.09–1.34, P<0.001) increased risk for CAD in Caucasian population;(2) In Han and Uygur population in Xinjiang, the distribution frequency of DD homozygotes of NFKB1 gene in CAD group was significantly higher than that in control group(all P < 0.001). NFKB1-94ins/del polymorphism was consistently associated with CAD risk in a recessive model after adjustment for cardiovascular risk factors in Xinjiang Han and Uygur population(OR=1.505, P=0.001; OR=1.534, P=0.001, respectively). The distribution of haplotype A-C-C built by rs3138053-rs2233406-rs2233409 was significantly higher in controls than in CAD cases in Hazark female population, it was still a protect factor for CAD after adjustment for cardiovascular risk factors in Hazark female population;(3) SCAD cases had significantly higher plasma levels of IL-6 compared to controls(P<0.001). General linear model analysis showed rs28362491 was independently associated with increased IL-6 levels by analyses of a recessive model(P<0.001) after adjustment for covariates. Conclusions:(1) NFKB1-94ins/del ATTG polymorphism was associated with susceptibility to CAD in Asian and Caucasian population.(2) In Han and Uygur population in Xinjiang, the DD genotype of rs28362491 was a risk marker for CAD. In the Hazark female population, the haplotype A-C-C built by rs3138053-rs2233406-rs2233409 was a protect factor for CAD.(3) NFKB1-94ins/del ATTG polymorphism was functionally associated with IL-6 expression, suggesting a mechanistic link between NFKB1-94ins/del ATTG polymorphism and CAD susceptibility. |
PDF Full Text Request