Common variants in the LAMA5 gene associate with fasting plasma glucose and serum triglyceride levels in a cohort of pre-and early pubertal children.
Common variants in the LAMA5 gene associate with fasting plasma glucose and serum triglyceride levels in a cohort of pre-and early pubertal children.
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DOI：
10.3233/pge-12036
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发表时间：
2012-10-01
影响因子：
0.4
通讯作者：
Fernandez JR
中科院分区：
文献类型：
--
作者：
De Luca M;Chandler-Laney PC;Wiener H;Fernandez JR
层粘连蛋白是在基底膜中发现的大的糖蛋白，它们在组织结构和细胞行为中起着至关重要的作用。以前，我们报道了两个LAMA 5多态性（rs659822和rs 944895）与绝经前妇女和老年受试者的人体测量特征，空腹血脂谱和血糖水平的关联。此外，早期在小鼠中的研究表明，Lama 5参与怀孕期间的器官形成和胎盘功能。本研究的目的是调查LAMA 5 rs659822或rs 944895是否与儿童出生体重以及人体测量、空腹血脂和空腹血糖水平的个体间变异性相关。研究对象为289名7-12岁的健康儿童，他们来自欧洲、西班牙和非洲裔美国人。共显性模型调整的遗传混合，年龄，性别和青春期阶段被用来测试与每个性状的多态性的关联。我们的分析显示，在Bonferroni校正多重测试后，rs659822与空腹血糖水平（p = 0.0004）和rs 944895与空腹血清甘油三酯（p = 0.004）显著相关。我们的研究结果证实了我们之前的发现，即LAMA 5的遗传变异有助于代谢表型的变化，并提供了这可能发生在生命早期的证据。
Laminins are large glycoproteins found in basement membranes where they play a vital role in tissue architecture and cell behavior. Previously, we reported the association of two LAMA5 polymorphisms (rs659822 and rs944895) with anthropometric traits, fasting lipid profile, and plasma glucose levels in pre-menopausal women and elderly subjects. Furthermore, earlier work in mice showed that Lama5 is involved in organogenesis and placental function during pregnancy. The objective of this study was to investigate whether LAMA5 rs659822 or rs944895 are associated with inter-individual variability in birth weight as well as anthropometric, fasting lipid profile, and fasting glucose levels in children. Two hundred and eighty nine healthy children aged 7–12 years of European, Hispanic, and African-American ancestry were studied. Co-dominant models adjusted for genetic admixture, age, gender, and stages of puberty were used to test for the association of the polymorphisms with each trait. Our analysis showed significant associations of rs659822 with fasting plasma glucose levels (p = 0.0004) and of rs944895 with fasting serum triglycerides (p = 0.004) after Bonferroni correction for multiple testing. Our results corroborate our previous findings that genetic variants in LAMA5 contribute to variation in metabolic phenotypes and provide evidence that this may occur early in life.