Association of a common LAMA5 variant with anthropometric and metabolic traits in an Italian cohort of healthy elderly subjects.
Association of a common LAMA5 variant with anthropometric and metabolic traits in an Italian cohort of healthy elderly subjects.
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DOI：
10.1016/j.exger.2010.10.003
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发表时间：
2011-01
影响因子：
3.9
通讯作者：
Rose, Giuseppina
中科院分区：
文献类型：
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作者：
De Luca, Maria;Crocco, Paolina;Wiener, Howard;Tiwari, Hemant K.;Passarino, Giuseppe;Rose, Giuseppina
关键词：
层粘连蛋白是在基底膜中发现的大的异源三聚体糖蛋白，其中它们在各种细胞类型的细胞-基质粘附、迁移、生长和分化中起重要作用。先前的工作报告，位于LAMA 5内含子1（rs659822）内的遗传变异与绝经前妇女队列中的人体测量特征和HDL-胆固醇水平相关。本研究旨在研究LAMA 5 rs659822对667名健康老年受试者（年龄64-107岁）的意大利队列中的人体测量特征、脂质谱和空腹血糖水平的影响。我们还测试了这些性状与单核苷酸多态性（SNP）rs 13043313之间的关联，该多态性先前被证明可以控制高加索人肝脏中LAMA 5转录本丰度的变化。在年龄和性别调整的线性回归分析中，我们没有发现rs 13043313与任何性状的关联。然而，在加性模型下，LAMA 5 rs659822的次要C等位基因与较矮的身材（p =0.007）和较高的空腹血糖水平（p = 0.02）相关。此外，假设隐性模型，与携带至少一个T等位基因的受试者相比，C等位基因纯合子受试者的总胆固醇（p = 0.034）和LDL-胆固醇（p = 0.016）水平分别平均低6%和10%。最后，在按年龄组（年龄范围64-89岁和90-107岁）分层的分析中，我们发现C-等位基因与64-89岁年龄组的体重增加呈相加相关（p = 0.018），而在年龄组中没有发现相关性90-107岁。总之，这项研究提供了LAMA 5 rs659822调节老年人人体测量和代谢特征的证据。未来的研究有必要在独立和更大的人群中复制这些发现，并调查rs659822是否是导致观察到的相关性的因果变异。
Laminins are large heterotrimeric glycoproteins found in basement membranes where they play an essential role in cell-matrix adhesion, migration, growth, and differentiation of various cell types. Previous work reported that a genetic variant located within the intron 1 of LAMA5 (rs659822) was associated with anthropometric traits and HDL-cholesterol levels in a cohort of premenopausal women. The present study aimed to investigate the effect of LAMA5 rs659822 on anthropometric traits, lipid profile, and fasting glucose levels in an Italian cohort of 667 healthy elderly subjects (aged 64–107 years). We also tested for association between these traits and the single nucleotide polymorphism (SNP) rs13043313, which was previously shown to control variation in LAMA5 transcript abundance in the liver of Caucasians. In age- and gender-adjusted linear regression analyses, we did not find association of rs13043313 with any of the traits. However, under an additive model, the minor C-allele of LAMA5 rs659822 was associated with shorter stature (p =0.007) and higher fasting glucose levels (p = 0.02). Moreover, subjects homozygous for the C-allele showed on average 6% and 10% lower total cholesterol (p = 0.034) and LDL-cholesterol (p = 0.016) levels, respectively, than those carrying at least one T allele, assuming a recessive model. Finally, in analyses stratified by age groups (age range 64–89 and 90–107 years), we found that the C-allele was additively associated with increased body weight (p = 0.018) in the age group 64–89 years, whereas no association was found in the age group 90–107 years. In conclusion, this study provides evidence that LAMA5 rs659822 regulates anthropometric and metabolic traits in elderly people. Future studies are warranted to replicate these findings in independent and larger populations and to investigate whether rs659822 is the causal variant responsible for the observed associations.
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影响因子：
3.6
作者：
Durbeej, Madeleine
通讯作者：
Durbeej, Madeleine
影响因子：
6.9
作者：
Candiello, Joseph;Cole, Gregory J.;Halfter, Willi
通讯作者：
Halfter, Willi
影响因子：
--
作者：
Labat-Robert, J
通讯作者：
Labat-Robert, J
影响因子：
6.5
作者：
Li, WD;Dong, CH;Price, RA
通讯作者：
Price, RA
摩洛哥南部人类白细胞基因表达变异的地理基因组学。
影响因子：
30.8
作者：
通讯作者：
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