Larsen L H, Rose C S, Sparsø T, Overgaard J, Torekov S S, Grarup N, Jensen D P, Albrechtsen A, Andersen G, Ek J, Glümer C, Borch-Johnsen K, Jørgensen T, Hansen T, Pedersen O
Steno Diabetes Center, Gentofte, Denmark.
Int J Obes (Lond). 2007 Feb;31(2):365-70. doi: 10.1038/sj.ijo.0803408. Epub 2006 Jun 6.
The estrogen-related receptor alpha (ERRalpha or NR3B1) is a transcription factor from the nuclear receptor super-family, group III. The gene encoding ERRalpha (ESRRA) is located on chromosome 11q13, a region showing genetic linkage to body mass index and fat percentage. Through interaction with the peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha), ERRalpha regulates key enzymes involved in the beta-oxidation of fatty acids.
By screening 48 overweight or obese subjects for variants in the exons, exon-intron boundaries and 1000 base pairs (bp) of the promoter region of ESRRA using bi-directional nucleotide sequencing, we identified seven variants. Four rare variants had minor allele frequencies (MAF) below 1%: Pro369Pro, Gly406Asp, 3'UTR+418G>A, 3'UTR+505C>A. Two single-nucleotide polymorphisms, Pro116Pro and IVS6+65C>T (MAF 15%), were in complete linkage disequilibrium (LD) (r (2)=1). We also confirmed the presence of a reported 23 bp microsatellite repeat (ESRRA23). The Pro116Pro and ESRRA23 variants were not associated with obesity, type 2 diabetes or related phenotypes in a large population-based study of 6365 Danish whites. The two variants were examined for interactions with variants in the peroxisome proliferator-activated receptor-gamma coactivator-1alpha and -beta; however, no evidence of epistatic effects between the variants was demonstrated.
The ESRRA23 and Pro116Pro variants of the gene encoding ERRalpha are not associated with obesity, type 2 diabetes or related quantitative traits in the examined Danish whites.
雌激素相关受体α（ERRα或NR3B1）是核受体超家族III组的一种转录因子。编码ERRα的基因（ESRRA）位于11号染色体q13区，该区域与体重指数和脂肪百分比存在遗传连锁关系。通过与过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）相互作用，ERRα调节参与脂肪酸β氧化的关键酶。
通过双向核苷酸测序对48名超重或肥胖受试者的ESRRA外显子、外显子-内含子边界和启动子区域的1000个碱基对（bp）中的变体进行筛查，我们鉴定出7个变体。4个罕见变体的次要等位基因频率（MAF）低于1%：Pro369Pro、Gly406Asp、3'UTR + 418G>A、3'UTR + 505C>A。两个单核苷酸多态性Pro116Pro和IVS6 + 65C>T（MAF为15%）处于完全连锁不平衡（LD）状态（r² = 1）。我们还证实了一个已报道的23 bp微卫星重复序列（ESRRA23）的存在。在一项对6365名丹麦白人进行的基于人群的大型研究中，Pro116Pro和ESRRA23变体与肥胖、2型糖尿病或相关表型无关。对这两个变体与过氧化物酶体增殖物激活受体γ共激活因子1α和β中的变体的相互作用进行了检测；然而，未证明这些变体之间存在上位效应的证据。
在检测的丹麦白人中，编码ERRα的基因的ESRRA23和Pro116Pro变体与肥胖、2型糖尿病或相关数量性状无关。
