ALOX12 polymorphisms are associated with fat mass but not peak bone mineral density in Chinese nuclear families

Abstract

Objective: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.Methods: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).Results: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.Conclusions: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.

Polymorphisms in inflammation associated genes ALOX15 and IL-6 are associated with bone properties in young women and fracture in elderly

“…Epidemiological studies have reported associations, albeit inconsistent, between genetic variation in both the ALOX12 and ALOX15 genes and bone properties [15--20], and with body Page 4 of 20 composition and fat mass [21,22]. Strengthening their putative role as candidate genes for osteoporosis, ALOX12/15 metabolites can act as ligands for peroxisome proliferator--activated receptor gamma (PPARγ) [23].…”

Association of ALOX15 gene polymorphisms with obesity-related phenotypes in Chinese nuclear families with male offspring

“…Therefore, lipoxygenase pathways may play an important role in the development of obesity. Indeed, previous studies have identified ALOX5 [28,29] and ALOX12 [14] as susceptibility genes for obesity. ALOX15, another member of the lipoxygenases family, has been linked to obesity risk in several studies [13] .…”

“…The human 12/15 lipoxygenase is encoded by arachidonate lipoxygenase 12/15 (ALOX12/15), both of which are located on chromosome 17p13, a region that is linked to obesity-related traits in several independent studies [13] . More recently, we have shown that genetic variation in ALOX12 is associated with total fat mass (TFM) in young Chinese men [14] . An analysis of tar ALOX12 cDNA showed that ALOX12 raised 12-HETE and 15-HETE levels but had a greater effect on 12-HETE [15] .…”

“…All of the male offspring were healthy. Exclusion criteria were the same as previously reported [14,17] . All the study subjects belonged to the Chinese Han ethnic group and were residents of Shanghai which is located approximately halfway along the coast of China.…”

Association of single nucleotide polymorphism Rs2236518 in PRDM16 gene with BMI in Chinese males

“…We also collected information on menses, obstetrical history, and history of hormonal contraceptive use in the female subjects. Exclusion criteria were the same as in our previous studies [14] . The study was approved by the Ethics Committee of the Shanghai Jiao Tong University Affiliated Sixth People's Hospital.…”