Genome-wide linkage of plasma adiponectin reveals a major locus on chromosome 3q distinct from the adiponectin structural gene - The IRAS family study
Genome-wide linkage of plasma adiponectin reveals a major locus on chromosome 3q distinct from the adiponectin structural gene - The IRAS family study
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DOI：
10.2337/db05-0428
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发表时间：
2006-06-01
期刊：
影响因子：
7.7
通讯作者：
Rotter, Jerome I.
中科院分区：
文献类型：
--
作者：
Guo, Xiuqing;Saad, Mohammed F.;Rotter, Jerome I.
脂联素(APM1)是一种脂肪细胞来源的多肽，可促进糖、脂和能量的稳态。我们评估了通过胰岛素抵抗动脉粥样硬化研究家族研究登记的西班牙裔美国人和非裔美国人家庭中血浆脂联素的遗传基础。10 cM基因组扫描分两批进行：由66个家庭(45个西班牙裔美国人和21个非裔美国人)组成的原始集合(集合1)和由66个家庭(45个西班牙裔美国人和21个非裔美国人)组成的复制集合(集合2)。用放射免疫法对132个家系中的131个个体的1,727个个体的脂联素水平进行了测定。在有和没有糖尿病受试者的集合1、集合2和集合集合(集合I+集合2)中，分别对西班牙裔美国人和非裔美国人进行了连锁分析。在西班牙裔美国人样本中，一个主基因被定位在3q27上，赔率对数(LOD)得分为8.21。对96名无血缘关系的个体进行了APMI基因的多态性筛查，并对拉美裔美国人样本中的18个单核苷酸多态(SNPs)进行了基因分型。血浆脂联素水平与两个SNPs及其伴发的单倍型有一定的相关性。然而，在连锁分析中结合其中一个或两个SNP并不能显著降低LOD得分。因此，3q27上的一个数量性状基因座可能与APM1基因不同，导致了拉美裔美国人血浆脂联素水平的变化。
Adiponectin (APM1) is an adipocyte-derived peptide that contributes to glucose, lipid, and energy homeostasis. We assessed the genetic basis of plasma adiponectin in Hispanic-American and African-American families enrolled through the Insulin Resistance Atherosclerosis Study Family Study. A 10-cM genome scan was performed in two batches: an original set (set 1) consisting of 66 families (45 Hispanic American and 21 African American) and a replication set (set 2) consisting of 66 families (45 Hispanic American and 21 African American). Adiponectin levels were measured by radioimmunoassay in 1,727 individuals from 131 of 132 families. Linkage analysis was carried out in Hispanic Americans and African Americans separately in set 1, set 2, and the pooled set (set I plus set 2), with and without diabetic subjects. A major gene was mapped to 3q27 with a logarithm of odds (LOD) score of 8.21 in the Hispanic-American sample. Ninety-six unrelated individuals were screened for polymorphisms in the APMI gene, and 18 single nucleotide polyporphisms (SNPs) were genotyped in the Hispanic-American sample. Plasma adiponeetin level was modestly associated with two SNPs and their accompaning haplotypes. Incorporating each or both SNPs in the linkage analysis, however, did not significantly re- duce the LOD score. Therefore, a quantitative trait locus at 3q27, likely distinct from the APM1 gene, contributes to the variation of plasma adiponectin levels in the Hispanic-American population.