C-reactive protein genotypes and haplotypes, polymorphisms in NSAID-metabolizing enzymes, and risk of colorectal polyps.
C-reactive protein genotypes and haplotypes, polymorphisms in NSAID-metabolizing enzymes, and risk of colorectal polyps.
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DOI：
10.1097/fpc.0b013e32831bd976
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发表时间：
2009-02
影响因子：
2.6
通讯作者：
Ulrich CM
中科院分区：
文献类型：
--
作者：
Poole EM;Bigler J;Whitton J;Sibert JG;Potter JD;Ulrich CM
C 反应蛋白 (CRP) 是与心血管疾病和可能的结肠癌相关的炎症的非特异性标志物。 CRP 多态性与健康成人中不同的 CRP 浓度相关，有一些证据表明 CRP 表达具有功能性影响。基于连锁不平衡的 tagSNP 选择算法识别了欧洲人的 6 个 tagSNP（−821A>G、−390C>T/A 90A>T 838G>C 2043G>A 和 4363C>A），定义了 6 个频率 >1% 的单倍型。在腺瘤性息肉 (n=491) 或增生性息肉 (n=184) 与无息肉对照 (n=583) 的病例对照研究中，我们研究了这些 SNP 与结直肠息肉风险的关系。具有 838 GC 或 CC 基因型的个体患腺瘤的风险略有增加，尽管没有统计学意义（OR=1.4 95% CI 0.9-2.1），并发腺瘤和增生性息肉的风险增加近 2 倍（OR=2.0 95% CI 1.1-3.6）。单倍型 ACACAC 还观察到并发腺瘤和增生性息肉的风险增加。没有检测到其他主要关联。与 2043G>A 相关的腺瘤风险因 NSAID 使用情况而异。在非甾体抗炎药非使用者中，有人认为 GA 或 AA 基因型与腺瘤风险降低相关；这在 NSAID 使用者中没有出现（p-交互作用 = 0.03）。我们还观察到 UGT1A1 [TA](7) 启动子重复多态性与 CRP tagSNP -390C>T/A 和 90A>T 之间的相互作用，其中只有纯合变异 CRP 基因型与 UGT1A1 6rpt/6rpt 基因型患者中腺瘤风险增加相关（-390C>T/A 的 p 相互作用 = 0.02 和 0.04，分别为90A>T）。这些结果为 CRP 遗传变异与结直肠息肉风险之间的关联提供了有限的支持。应进一步评估观察到的相互作用。
C-reactive protein (CRP) is a non-specific marker of inflammation linked to cardiovascular disease and possibly colon cancer. Polymorphisms in CRP have been associated with differential CRP concentrations among healthy adults, with some evidence for functional effects on CRP expression. A linkage-disequilibrium-based tagSNP-selection algorithm identified six tagSNPs for Europeans (−821A>G, −390C>T/A 90A>T 838G>C 2043G>A and 4363C>A), defining 6 haplotypes >1% frequency. In a case-control study of adenomatous (n=491) or hyperplastic (n=184) polyps vs. polyp-free controls (n=583) we investigated these SNPs in relation to colorectal polyp risk. Individuals with 838 GC or CC genotypes had a modestly, although not statistically significantly, increased risk of adenomas (OR=1.4 95% CI 0.9-2.1) and a nearly 2-fold increased risk of concurrent adenomas and hyperplastic polyps (OR=2.0 95% CI 1.1-3.6). Increased risk for concurrent adenomas and hyperplastic polyps was also observed for haplotype ACACAC. No other main associations were detected. Risk of adenomas associated with 2043G>A differed with NSAID use. Among NSAID non-users, there was a suggestion that the GA or AA genotypes were associated with decreased risk of adenomas; this was not seen among NSAID users (p-interaction = 0.03). We also observed interactions between UGT1A1 [TA](7) promoter repeat polymorphism and CRP tagSNPs −390C>T/A and 90A>T, in which only the homozygous variant CRP genotype was associated with increased adenoma risk among those with the UGT1A1 6rpt/6rpt genotype (p-interaction= 0.02 and 0.04 for −390C>T/A and 90A>T, respectively). These results provide limited support for associations between genetic variation in CRP and colorectal polyp risk. The observed interactions should be evaluated further.