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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.

Alendronate is an antiosteoporotic drug that targets the mevalonate pathway. To investigate whether the genetic variations in this pathway affect the clinical efficacy of alendronate in postmenopausal Chinese women with osteopenia or osteoporosis, 23 single-nucleotide polymorphisms (SNPs) in 7 genes were genotyped in 500 patients treated with alendronate for 12 months. Bone mineral density (BMD) was measured at baseline and after 12 months. The rs10161126 SNP in the 3' flanking region of MVK and the GTCCA haplotype in FDFT1 were significantly associated with therapeutic response. A 6.6% increase in BMD in the lumbar spine was observed in the GG homozygotes of rs10161126; AG heterozygotes and AA homozygotes experienced a 4.4 and 4.5% increase, respectively. The odds ratio (95% confidence interval) of G allele carriers to be responders in lumbar spine BMD was 2.06 (1.08-6.41). GTCCA haplotype in FDFT1 was more frequently detected in the group of responders than in the group of non-responders at the total hip (2.6 vs 0.5%, P=0.009). Therefore, MVK and FDFT1 polymorphisms are genetic determinants for BMD response to alendronate therapy in postmenopausal Chinese women.

Objective: To assess rhabdomyolysisassociated skeletal muscle changes induced by complete ischaemia in rabbits using MRI.Methods: Acute ischaemia was induced in the right hind limb of 34 New Zealand white rabbits by arterial ligation. MRI of vastus lateralis was carried out pre-operatively and every hour post-operatively up to 7 h. T 1 weighted images, T 2 weighted images with fat suppression, T 2 maps and diffusion tensor scans were obtained. The correlation of MRI findings with histopathological changes in biopsies of vastus lateralis was examined.Results: Histopathology demonstrated early cellular oedema 1 h post ischaemia and irreversible injuries by 7 h, including loss of striation and broken muscle fibres. T 2 weighted images with fat suppression showed inhomogeneous high signal intensity of vastus lateralis, which progressively increased from 2 h following ischaemia. The T 2 relaxation rate of ischaemic vastus lateralis was significantly greater than normal muscle (p,0.001) and demonstrated a linear increase with time following ischaemia. A similar linear increase was also found in the ischaemic vastus lateralis apparent diffusion coefficient (ADC) 1-5 h post ischaemia (p50.006). Both the T 2 ADC and fractional anisotropy (FA) were significantly higher on the ischaemic side 7 h post ischaemia (for T 2 , p50.02; for ADC, p50.004). Conclusion:Muscle oedema is detectable on MR images and is reflected well by T 2 , ADC and FA values. MRI may have value in clinical evaluation of rhabdomyolysis. Advances in knowledge:Ischaemic changes detected by MRI may have value in the diagnosis of rhabdomyolysis.

Purpose Whether Tsukushi (TSK) can protect against high-fat diet (HFD)-induced obesity and improve glucose metabolism remains controversial. Serum levels of TSK in the population have not been reported until now. We assessed the association among TSK level, TSKU genotype, and metabolic traits in humans. Methods Associations between serum TSK levels and metabolic traits were assessed in 144 Han Chinese individuals. Loci in the TSKU gene region were further genotyped in 11,022 individuals. The association between the loci and serum TSK level was evaluated using the additive genetic model. The association between the loci and their metabolic traits in humans were also verified. Results Lower TSK levels were observed in obese subjects than in control subjects (median and interquartile range 17.78:12.07–23.28 vs. 23.81:12.54–34.56, P < 0.05). However, in obese subjects, TSK was positively associated with BMI (β ± SE: 0.63 ± 0.31, P = 0.049), visceral fat area (β ± SE: 12.15 ± 5.94, P = 0.011), and deterioration of glucose metabolism. We found that rs11236956 was associated with TSK level in obese subjects (β 95% CI 0.17, 0.07–0.26; P = 0.0007). There was also a significant association between rs11236956 and metabolic traits in our population. Conclusions Our findings showed that serum TSK levels were associated with metabolic disorders in obese subjects. We also identified rs11236956 to be associated with serum TSK levels in obese subjects and with metabolic disorders in the total population.

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