exploring the interface between bone and fat at the molecular and genetic levels may improve our understanding of osteoporosis and obesity, which may lead to new interventions and treatments. Body weight is determined mostly by fat, muscle and bone mass. Body composition assessment by dual-energy X-ray absorptiometry (DXA) is a readily accessible, inexpensive and non-invasive method. DXA detects total body mineral mass, total fat mass (TFM) and total lean mass (TLM). The relationships between bone mass and TFM and TLM have been examined, although the results are controversial.10–12 Studies have also shown several genomic regions that influence both obesity and osteoporosis.13,14 Although various candidate genes have been identified that may contribute to BMD, far less is known about genes affecting obesity phenotypes such as BMI, TLM and TFM. Recently, Klein et al.15 suggested that mouse arachidonate 15-lipoxygenase (ALOX15) could negatively regulate peak bone mass. Compared with control mice, ALOX15 knockout mice have a higher BMD, and pharmacologic inhibitors of ALOX15 improve the BMD and bone strength in a model of osteoporosis. It has also been reported that overexpression of human ALOX15 in transgenic rabbits protects against bone loss.16 However, based on the products of their lipoxygenase reactions, mouse ALOX15 is functionally more similar to human ALOX12.17,18 Therefore, human ALOX12 might represent a strong candidate gene for susceptibility to osteoporosis. In fact, a positive correlation between ALOX12 gene polymorphisms and BMD in human beings has been established by previous studies,19–21 although all the studies were limited to Caucasian samples. So far, no such data have been reported for an Asian population. Moreover, most previous studies of candidate genes have been performed in women, with only one study focusing on men. The human ALOX12 gene is composed of 14 exons and 13 introns, mapping to chromosome 17p13, a region that is thought to be associated with body mass index (BMI) (http:// obesitygene.pbrc.edu). Furthermore, ALOX12 has an impor- tant function in obesity-related complex phenotypes, inclu- ding hypertension, diabetes, atherosclerosis and insulin secretion.22–24 However, the relationship between ALOX12 and obesity has never been studied. In this study, we performed family-based-association analyses on all six tagging single-nucleotide polymorphisms (SNPs) in the ALXO12 gene using the quantitative transmission disequili- brium test (QTDT) to determine whether SNPs and haplo- types in ALXO12 were associated with peak BMD variations and obesity-related phenotypes in a large sample of Chinese males in nuclear families. Materials and methods Subjects We recruited 1296 individuals from 427 Chinese nuclear families with male offspring from 2004 to 2007. The average ALOX12 polymorphisms are associated with fat mass in men W-J Xiao et al family size was 3.03, as 402 and 25 families had 1 and 2 children, respectively. Every study subject completed a questionnaire concerning age, sex, medical history, family history, marital status, physical activity, alcohol use, diet habits and smoking history. All male offspring were healthy. The following criteria were used to exclude individuals from the study: (1) serious effects from cerebrovascular disease; (2) diabetes mellitus; (3) chronic renal disease; (4) serious chronic liver disease or alcoholism; (5) significant chronic lung disease; (6) corticosteroid therapy at pharmacologic levels for 43 months; (7) treatment with anticonvulsant therapy for 46 months; (8) evidence of other metabolic or inherited bone diseases such as hyper- or hypoparathyroid- ism, Paget’s disease of the bone, osteomalacia, osteogenesis imperfecta or others; (9) rheumatoid arthritis or collagen disease; (10) recent major gastrointestinal disease (within the past year) such as peptic ulcer, malabsorption, chronic ulcerative colitis, regional enteritis or any significant chronic diarrhea state; (11) significant disease of any endocrine organ that would affect bone mass; (12) hyperthyroidism and (13) any neurological or musculoskeletal condition that would be a non-genetic cause of low bone mass. All study subjects belonged to the Chinese Han ethnic group. All were residents of Shanghai City, located on the mid-eastern coast of China. The study was approved by the ethics committee of the Shanghai Jiao Tong University Affiliated Sixth People’s Hospital. All subjects signed informed consent documents before entering the study. BMD and body composition measurements The BMD of the lumbar spine 1–4, the left proximal femur (including the femoral neck and the total hip), as well as TFM and TLM were measured by DXA on a GE-LUNAR Prodigy (Lunar Corp., Madison, WI, USA) in fan-beam mode. All subjects were measured for BMD, and all sons were also measured for TFM and TLM. The machine was calibrated daily, and the coefficient of variability values of the DXA measurements (which were obtained from 15 individuals repeated three times) were 1.39% for the lumbar spine, 2.22% for the femoral neck and 0.70% for the total hip. The coefficient of variabilities were 1.18 and 3.72% for TLM and LFM, respectively. The long-term reproducibility of our DXA data during the trial, based on weekly repeated phantom measurements using standardized equipment, was 0.45%. BMI is defined as body weight/height2 (kg m–2). The percentage fat mass (PFM) is the ratio of TFM to body weight. Genotyping SNPs located within the ALOX12 gene were selected from the NCBI LocusLink (http://Ncbi.nlm.nih.gov/LocusLink) and HapMap (http://hapmap.org). Polymorphisms spanning the ALOX12 gene were selected from the SNPs resource based on the estimated pairwise linkage disequilibrium (LD), r2, between all common SNPs. The algorithm bins SNPs whose 379 International Journal of Obesity