IGF-I and IGFBP-3 polymorphisms in relation to circulating levels among African American and Caucasian women.
IGF-I and IGFBP-3 polymorphisms in relation to circulating levels among African American and Caucasian women.
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DOI：
10.1158/1055-9965.epi-08-0856
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发表时间：
2009-03
期刊：
影响因子：
--
通讯作者：
Baird DD
中科院分区：
文献类型：
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作者：
D'Aloisio AA;Schroeder JC;North KE;Poole C;West SL;Travlos GS;Baird DD
循环中胰岛素样生长因子-1（IGF-I）和胰岛素样生长因子结合蛋白-3（IGFBP-3）水平与常见疾病有关。虽然基于家族的研究表明，遗传变异有助于循环IGF-I和IGFBP-3水平，但与多个IGF-I和IGFBP-3单核苷酸多态性（SNP）的关联分析有限，特别是在非洲裔美国人中。我们评估了30个IGF-I和15个IGFBP-3单核苷酸多态性，并在984名绝经前非洲裔美国人和白人妇女中估计了与血浆IGF-I和IGFBP-3相关的二倍体型。在两个种族中，IGFBP-3 rs 2854746 Ala 32 Gly与IGFBP-3呈正相关（白人中CC与GG的平均差异= 631 ng/ml，95%置信区间：398，864;非裔美国人= 897 ng/ml，95%置信区间：656，1138），和IGFBP-3双倍型与rs 2854746 GG基因型具有较低的平均IGFBP-3水平比参考双倍型与CG基因型，而IGFBP-3双倍型与CC基因型具有较高的平均IGFBP-3水平。IGFBP-3 rs 2854744（−202 A/C）仅在高加索人中与rs 2854746存在强连锁不平衡，但在两个种族中均与血浆IGFBP-3相关。另外8个IGFBP-3 SNP与平均IGFBP-3水平的5%或更大差异相关，种族之间的相关性基本一致。12个IGF-I SNPs与平均IGF-I水平的10%或更大差异相关，但种族间的相关性通常不一致。与血浆IGF-I的二倍型关联并不平行IGF-I SNP关联。我们的研究支持常见的IGFBP-3 SNPs，特别是rs 2854746，影响非裔美国人和高加索人的血浆IGFBP-3水平，但提供的证据较少IGF-I SNPs影响血浆IGF-I水平。
Circulating insulin-like growth factor-one (IGF-I) and IGF binding protein-3 (IGFBP-3) levels have been associated with common diseases. Although family-based studies suggest that genetic variation contributes to circulating IGF-I and IGFBP-3 levels, analyses of associations with multiple IGF-I and IGFBP-3 single nucleotide polymorphisms (SNPs) have been limited, especially among African Americans. We evaluated 30 IGF-I and 15 IGFBP-3 SNPs and estimated diplotypes in association with plasma IGF-I and IGFBP-3 among 984 premenopausal African American and Caucasian women. In both races, IGFBP-3 rs2854746 (Ala32Gly) was positively associated with plasma IGFBP-3 (CC versus GG mean difference among Caucasians = 631 ng/ml, 95% confidence interval: 398, 864; African Americans = 897 ng/ml, 95% confidence interval: 656, 1138), and IGFBP-3 diplotypes with the rs2854746 GG genotype had lower mean IGFBP-3 levels than referent diplotypes with the CG genotype, while IGFBP-3 diplotypes with the CC genotype had higher mean IGFBP-3 levels. IGFBP-3 rs2854744 (−202 A/C) was in strong linkage disequilibrium with rs2854746 in Caucasians only, but was associated with plasma IGFBP-3 in both races. Eight additional IGFBP-3 SNPs were associated with 5% or greater differences in mean IGFBP-3 levels, with generally consistent associations between races. Twelve IGF-I SNPs were associated with 10% or greater differences in mean IGF-I levels, but associations were generally discordant between races. Diplotype associations with plasma IGF-I did not parallel IGF-I SNP associations. Our study supports that common IGFBP-3 SNPs, especially rs2854746, influence plasma IGFBP-3 levels among African Americans and Caucasians, but provides less evidence that IGF-I SNPs affect plasma IGF-I levels.