Genetic determinants of adiponectin regulation revealed by pregnancy.
Genetic determinants of adiponectin regulation revealed by pregnancy.
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DOI：
10.1002/oby.21805
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发表时间：
2017-05
期刊：
影响因子：
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通讯作者：
Lowe WL Jr
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文献类型：
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作者：
Hivert MF;Scholtens DM;Allard C;Nodzenski M;Bouchard L;Brisson D;Lowe LP;McDowell I;Reddy T;Dastani Z;Richards JB;Hayes MG;Lowe WL Jr
我们研究了妊娠期间脂联素的遗传决定因素，以揭示脂肪细胞调节的新生物学。我们对来自高血糖和不良妊娠结局 (HAPO) 研究的 1,322 名孕妇进行了一项全基因组关联研究，并在妊娠约 28 周时测量了脂联素。我们在两个复制队列中选择了达到 P<5x10−5 的变异体进行从头基因分型（妊娠和生长血糖调节遗传学 (Gen3G) N=522；ECOGENE-21 N=174）。在综合荟萃分析中，位于 chr3q25（靠近 LEKR1/CCNL1）的 rs900400 母体 T 等位基因与母体脂联素较低相关（每个风险等位基因脂联素的 β±SE= -0.18±0.03 SD；P=1.5x10−8；N=2004；多变量调整模型）。相比之下，在大量非孕妇样本中，rs900400 仅显示出与脂联素的名义相关性（β±SE= -0.012±0.006；P=0.05；N=16,678 名来自 ADIPOgen 联盟的女性）。后代rs900400 T风险等位基因与较大的新生儿皮褶厚度相关（每个风险等位基因β±SE=0.19±0.04 SD；P=4.1x10−8；N=1489）和较高的脐带血瘦素（每个风险等位基因β±SE=0.28±0.05 log-瘦素；P=8.2x10−9；N=502），但与脐带血无关脂联素（P=0.23；N=495）。 rs900400 的 T 等位基因与脂肪细胞中 TIPARP 的较高表达相关。我们对怀孕期间和生命早期脂肪因子的研究表明 rs900400 在脂肪细胞功能中发挥作用。
We investigated genetic determinants of adiponectin during pregnancy to reveal novel biology of adipocyte regulation. We conducted a genome-wide association study in 1,322 pregnant women from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study with adiponectin measured at ~28 weeks of gestation. We selected variants reaching P<5x10−5 for de novo genotyping in two replication cohorts (Genetics of Glycemic regulation in Gestation and Growth (Gen3G) N=522; ECOGENE-21 N=174). In the combined meta-analysis, the maternal T allele of rs900400 located on chr3q25 (near LEKR1/CCNL1) was associated with lower maternal adiponectin (β±SE= −0.18±0.03 SD of adiponectin per risk allele; P=1.5x10−8; N=2004; multivariable adjusted models). In contrast, rs900400 showed only nominal association with adiponectin in a large sample of non-pregnant women (β±SE= −0.012±0.006; P=0.05; N=16,678 women from the ADIPOgen consortium). Offspring rs900400 T risk allele was associated with greater neonatal skin fold thickness (β±SE=0.19±0.04 SD per risk allele; P=4.1x10−8; N=1489) and higher cord blood leptin (β±SE=0.28±0.05 log-leptin per risk allele; P=8.2x10−9; N=502), but not with cord blood adiponectin (P=0.23; N=495). T allele of rs900400 was associated with higher expression of TIPARP in adipocytes. Our investigations of adipokines during pregnancy and early life suggest that rs900400 has a role in adipocyte function.