A Single Nucleotide Polymorphism on Exon-4 of the Gene Encoding PPARδ Is Associated with Reduced Height in Adults and Children
A Single Nucleotide Polymorphism on Exon-4 of the Gene Encoding PPARδ Is Associated with Reduced Height in Adults and Children
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DOI：
10.1210/jc.2009-0392
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发表时间：
2009-07-01
影响因子：
5.8
通讯作者：
Palmer, Colin N. A.
中科院分区：
文献类型：
--
作者：
Burch, Lindsay R.;Zhou, Kaixin;Palmer, Colin N. A.
内容：过氧化物酶体增殖物激活受体（Peroxisome proliferator-activated receptor，PPAR-delta）是一种核转录因子，在能量代谢、脂类代谢、葡萄糖代谢等多种代谢过程中发挥重要作用。候选基因的研究已经确定了一个假定的功能变异，rs 2016520，在基因编码的过氧化物酶体增殖物激活受体δ（PPARD），这是在一些研究与代谢性状。此外，这种单核苷酸多态性与成人身高在几个全基因组扫描，但这种关联并没有实现全基因组significant.Objective：这项研究试图确定是否PPARD变异affectedheight.Design：单倍型标签分析跨PPARD进行了约11,000人从威康信托U。K. 2型糖尿病病例对照收集（Go-DARTS 2）。结果：在2型糖尿病患者和非糖尿病对照组中，rs 2016520与身高之间存在相关性（合并P = 5 × 10（-5））。在一项荟萃分析中，使用了来自高加索人群的已发表数据，共有超过38，000名参与者，发现了该基因座及其与身高相关性的令人信服的证据（P = 10（-8）），总体效应大小约为每个等位基因0.5 cm。在一组2700青春期前的儿童也表现出类似的效果大小，看到在adult.Conclusion：PPARD变异明显与表型的身材减少在成人和儿童类似的分析。由于身高是代谢和营养状况的重要指标，这为PPAR δ在关键代谢功能中的关键作用提供了额外的支持。PPAR δ可能通过多种机制影响身高，包括改变代谢效率或影响破骨细胞功能。（临床内分泌代谢杂志94：2587-2593，2009）
Context: Peroxisome proliferator-activated receptor (PPAR)-delta is a nuclear transcription factor that plays a key role in many metabolic processes, including energy metabolism, and lipid and glucose metabolism. Candidate gene studies have identified a putative functional variant, rs2016520, in the gene encoding PPAR delta ( PPARD), which is associated in some studies with metabolic traits. In addition, this single-nucleotide polymorphism was associated with adult height in several whole-genome scans, but this association did not achieve whole genome significance.Objective: This study sought to determine whether PPARD variation influenced height.Design: Haplotype tagging analysis across PPARD was performed in about 11,000 individuals from the Wellcome Trust U. K. Type 2 Diabetes Case Control Collection (Go-DARTS2).Results: There was an association between rs2016520 and height in both patients with type 2 diabetes and controls without diabetes (combined P = 5 X 10(-5)). In a metaanalysis using published data from Caucasian cohorts totaling more than 38,000 participants, compelling evidence was found for this locus and its association with height (P = 10(-8)) with an overall effect size of about 0.5 cm per allele. A similar analysis in a group of 2700 prepubescent children also displayed a similar effect size to that seen in the adults.Conclusion: PPARD variation is clearly associated with a phenotype of reduced stature in both adults and children. Because height is an important indicator of metabolic and nutritional status, this provides additional support for a key role for PPAR delta in critical metabolic functions. PPAR delta may affect height through a variety of mechanisms including altered metabolic efficiency or effects on osteoclast function. (J Clin Endocrinol Metab 94: 2587-2593, 2009)