Enquobahrie Daniel A, Rice Kenneth, Williams O Dale, Williams Michelle A, Gross Myron D, Lewis Cora E, Schwartz Stephen M, Siscovick David S
Cardiovascular Health Research Unit, Department of Epidemiology, University of Washington, Seattle, WA, USA.
Atherosclerosis. 2009 Feb;202(2):513-20. doi: 10.1016/j.atherosclerosis.2008.05.018. Epub 2008 May 18.
Interleukin-1B (IL1B) modulates C-reactive protein (CRP) expression. However, whether IL1B genetic variation is associated with CRP level is unknown. Further, obesity, a state of low-grade inflammation that influences cellular IL-1 functions may modify this association.
Study participants (N=3289), 48% blacks and 52% whites, had CRP level measurements at year 7 and year 15 examinations as part of the CARDIA study. Ten tag single nucleotide polymorphisms (SNPs) that characterize common IL1B gene variation were genotyped. In SNP analysis, no significant associations with either level or change in time CRP were observed after multiple testing adjustments. However, global ILIB gene variation was associated with year 7 to year 15 change in CRP (global nominal p=0.004, multiple testing corrected p=0.048) among obese blacks. Compared to the commonest haplotype, a common haplotype that includes the SNP rs1143642 was associated with greater increases in CRP from year 7 to year 15 among obese blacks and whites while another common haplotype that includes the SNP rs3917356 was associated with decreased change in CRP from year 7 to year 15 among obese blacks. The rare alleles of ILIB SNPs, SNP 7114 (rs1143642) and SNP 3298 (rs3917356), were associated with greater increases and decreases in CRP from year 7 to year 15 among blacks, respectively, compared to their common variants.
IL1B genetic variation may have a role in CRP level regulation and this association may be modified by obesity.
白细胞介素-1β(IL1B)可调节C反应蛋白(CRP)的表达。然而,IL1B基因变异是否与CRP水平相关尚不清楚。此外,肥胖作为一种影响细胞IL-1功能的低度炎症状态,可能会改变这种关联。
作为CARDIA研究的一部分,研究参与者(N = 3289)中48%为黑人,52%为白人,在第7年和第15年检查时测量了CRP水平。对表征常见IL1B基因变异的10个标签单核苷酸多态性(SNP)进行了基因分型。在SNP分析中,经过多次检验调整后,未观察到与CRP水平或随时间变化有显著关联。然而,在肥胖黑人中,IL1B基因的整体变异与第7年至第15年CRP的变化相关(整体名义p = 0.004,经多次检验校正p = 0.048)。与最常见的单倍型相比,包含SNP rs1143642的一种常见单倍型与肥胖黑人和白人从第7年到第15年CRP的更大增加相关,而另一种包含SNP rs3917356的常见单倍型与肥胖黑人从第7年到第15年CRP变化的减少相关。与常见变体相比,IL1B SNP的罕见等位基因,即SNP 7114(rs1143642)和SNP 3298(rs3917356),分别与黑人从第7年到第15年CRP的更大增加和减少相关。
IL1B基因变异可能在CRP水平调节中起作用,且这种关联可能会因肥胖而改变。