Department of Osteoporosis, Metabolic Bone Disease and Genetic Research Unit, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China.
Int J Obes (Lond). 2011 Mar;35(3):378-86. doi: 10.1038/ijo.2010.157. Epub 2010 Aug 10.
Arachidonate 12-lipoxygenase (ALOX12) is a member of the lipoxygenase superfamily, which catalyzes the incorporation of molecular oxygen into polyunsaturated fatty acids. The products of ALOX12 reactions serve as endogenous ligands for peroxisome proliferator-activated receptor γ (PPARG). The activation of the PPARG pathway in marrow-derived mesenchymal progenitors stimulates adipogenesis and inhibits osteoblastogenesis. Our objective was to determine whether polymorphisms in the ALOX12 gene were associated with variations in peak bone mineral density (BMD) and obesity phenotypes in young Chinese men.
All six tagging single-nucleotide polymorphisms (SNPs) in the ALOX12 gene were genotyped in a total of 1215 subjects from 400 Chinese nuclear families by allele-specific polymerase chain reaction. The BMD at the lumbar spine and hip, total fat mass (TFM) and total lean mass (TLM) were measured using dual-energy X-ray absorptiometry. The pairwise linkage disequilibrium among SNPs was measured, and the haplotype blocks were inferred. Both the individual SNP markers and the haplotypes were tested for an association with the peak BMD, body mass index, TFM, TLM and percentage fat mass (PFM) using the quantitative transmission disequilibrium test (QTDT).
Using the QTDT, significant within-family association was found between the rs2073438 polymorphism in the ALOX12 gene and the TFM and PFM (P=0.007 and 0.012, respectively). Haplotype analyses were combined with our individual SNP results and remained significant even after correction for multiple testing. However, we failed to find significant within-family associations between ALOX12 SNPs and the BMD at any bone site in young Chinese men.
Our present results suggest that the rs2073438 polymorphism of ALOX12 contributes to the variation of obesity phenotypes in young Chinese men, although we failed to replicate the association with the peak BMD variation in this sample. Further independent studies are needed to confirm our findings.
花生四烯酸 12-脂氧合酶（ALOX12）是脂氧合酶超家族的成员，它催化氧分子掺入多不饱和脂肪酸。ALOX12 反应的产物作为过氧化物酶体增殖物激活受体γ（PPARG）的内源性配体。骨髓间充质祖细胞中 PPARG 途径的激活刺激脂肪生成并抑制成骨细胞生成。我们的目的是确定 ALOX12 基因中的多态性是否与年轻中国男性的峰值骨密度（BMD）和肥胖表型的变化有关。
通过等位基因特异性聚合酶链反应，对来自 400 个中国核心家庭的 1215 名受试者的 ALOX12 基因中的 6 个标记单核苷酸多态性（SNP）进行了基因分型。使用双能 X 射线吸收法测量腰椎和髋部的 BMD、总脂肪量（TFM）和总瘦体重（TLM）。测量 SNP 之间的成对连锁不平衡，并推断单倍型块。使用定量传递不平衡测试（QTDT），分别用个体 SNP 标记物和单倍型检测与峰值 BMD、体重指数、TFM、TLM 和脂肪百分比（PFM）的关联。
使用 QTDT，在 ALOX12 基因中的 rs2073438 多态性与 TFM 和 PFM 之间发现了显著的家系内关联（P=0.007 和 0.012）。单体型分析与我们的个体 SNP 结果相结合，即使在经过多次测试校正后仍然显著。然而，我们未能发现 ALOX12 SNP 与年轻中国男性任何骨骼部位的 BMD 之间存在显著的家系内关联。
我们目前的结果表明，ALOX12 的 rs2073438 多态性导致年轻中国男性肥胖表型的变化，尽管我们未能在该样本中复制与峰值 BMD 变化的关联。需要进一步的独立研究来证实我们的发现。
Zotero 插件