The Association Between-94ins/del ATTG Polymorphism In The Promoter Region Of NFKB1 Gene And Coronary Artery Disease

Objective(1)To explore the association between NFKB1 promoter region-94 ins / del ATTG(rs28362491)gene polymorphism and susceptibility to coronary artery disease by systematic review and meta-analysis;(2)To investigate the NFKB1 promoter region-94 ins / del ATTG gene polymorphism and coronary artery disease in Han population of Gansu province.Methods(1)The studies for the association between-94 ins / del ATTG(rs28362491)polymorphism in the promoter region of NFKB1 gene and coronary artery disease were searched up to February 2016 from the databases of PubMed,Web of Science,VIP according to the search terms "NFKB1 gene","nuclear transcription factor-κB","coronary artery disease","coronary atherosclerotic heart disease","gene polymorphism",Then,the meta-analysis under the allele,homozygous,dominant and recessive genetic model was performed using Stata 11.0 software;(2)The case-control studies selected 250 cornary artery disease patients and 266 healthy subjects to detect the allele and genotype frequency of NFKB1(rs28362491)by polymerase chain reaction(PCR)-restriction fragment length polymorphism(RFLP)and verified by sequencing,NFKB1 promoter region-94 ins / del ATTG gene polymorphism and coronary artery disease susceptibility in Han population of Gansu province were analyzed by SPSS 19.0 statistical software.Results(1)Meta-analysis of 11 subjects included in the study showed that-94 ins / del ATTG polymorphism in the promoter region of NFKB1 gene was associated with susceptibility to coronary artery disease under allele(D vs I),homozygote(DD vs II),dominant(DD + ID vs II)and recessive(DD vs ID + II)gene model.The risk in the subjects carring D allele increased 28%(OR = 1.28,95% CI = 1.22~1.35,P<0.01)compared with those carrying the I allele.Comparison with II genotype,the risk of those with DD and DD+ID genotype increased 32%(OR=1.32,95%CI=1.19~1.47,P < 0.01)and 15%(OR=1.15,95%CI=1.07~1.24,P < 0.01).The risk of coronary artery disease in the subjects with DD genotype was significantly higher than that with ID + II genotype(OR=1.26,95%CI=1.15~1.38,P=0.002)under the recessive gene model.Subgroup analysis was performed according to the geographical distribution,the risk of coronaryartery disease under the above four gene models increased(OR=1.23,95%CI=1.15~1.32,P<0.01;OR=1.48,95%CI=1.29~1.70,P < 0.01;OR=1.16,95%CI=1.05~1.27,P=0.002;OR=1.43,95%CI=1.26~1.63,P<0.01)in Asian population.And the risk of coronary artery disease under the three gene models(D vs I,DD vs II,DD + ID vs II)increased in European population(OR =1.28,95% CI = 1.16 ~ 1.41,P <0.01;OR = 1.30,95% CI = 1.06~1.59,P = 0.011;OR = 1.19,95%CI = 1.04~1.37,P = 0.012).While the North American population was only relevant in the D vs I gene model(OR = 1.45,95%CI =1.29~1.64,P<0.01).Subgroup analysis was performed according to the ethcinity,the risk of coronary artery disease in the above four gene models increased(OR=1.24,95%CI=1.16~1.33,P < 0.01;OR=1.45,95%CI=1.26~1.67,P < 0.01;OR=1.14,95%CI=1.04~1.26,P=0.007;OR=1.42,95%CI=1.25~1.62,P < 0.01)in Asian population.While the risk of coronary artery disease in Caucasian population in three gene models(D vs I、DD vs II、DD + ID vs II)increased(OR=1.33,95%CI=1.23~1.43,P<0.01;OR=1.19,95%CI=1.02~1.38,P=0.027;OR=1.16,95%CI=1.05~1.29,P=0.004);(2)The frequency of genotype and allele distribution of NFKB1 promoter region-94 ins / del ATTG gene polymorphism in Han population of Gansu was statistically different from that in normal population,was associated with coronary artery disease genetic susceptibility,and the DD genotype increased risk of coronary artery disease.Subgroup analysis was performed according to gender,the NFKB1 promoter region-94ins/del ATTG gene polymorphism was associated with the genetic susceptibility of coronary artery disease in Han male population of Gansu.The risk of coronary artery disease in Gansu Han male population increased,but not relevant genetic susceptibility of coronary artery disease in Gansu Han female population.Conclusions(1)NFKB1 gene promoter region-94 ins / del ATTG gene polymorphism is significantly associated with coronary artery disease susceptibility,but mainly in population of Asian and European countries(subgroup analysis by geographical distribution)and Asian and Caucasian population(subgroup analysis by ethnicity).(2)The association of the NFKB1 promoter region-94 ins / del ATTG gene polymorphism in the total Gansu population,especially in male population was associated with the genetic susceptibility of coronary artery disease,the risk of coronary artery disease in population who carrying DD genotype was increased.