Linkage Exclusion Analyses Of Obesity-Related Phenotypes In Caucasian & Linkage And/or Association Analyses Of CASR Gene With BMD In Chinese

Leptin (LEP) and the uncoupling proteins 2/3 (UCP2/UCP3) are key molecules involved in the regulation of food intake and energy expenditure. However, studies employing largely the linkage and association approaches have generated controversial results concerning their genetic effects on obesity. The present study is to investigate whether chromosomal regions 7q and llq, which contain LEP and UCP2/UCP3, respectively, can be excluded for linkage with a variety of obesity-related phenotypes in a US Caucasian population. Body mass index (BMI), fat mass, percentage fat mass (PFM) were measured by dual-energy X-ray absorptiometry. Exclusion mapping using a variance component approach was employed in a sample of 1, 816 individuals coming from 79 extended Caucasian pedigrees. We were able to exclude chromosomal region 7q containing LEP as having an effect on fat mass and PFM at effect sizes of 5% or greater, and on BMI at effect sizes of 10% or greater. In addition, we were able to exclude chromosomal region llq containing UCP2/UCP3 as having an effect on fat mass and PFM at effect sizes of 10% or greater, and on BMI at effect sizes of 5% or greater. Our linkage exclusion analyses suggest that genetic variations in the LEP and UCP2/UCP3 genes are unlikely to have a substantial effect on variation in obesity phenotypes in thisparticular US Caucasian population.Bone mineral density (BMD), as an index of bone strength, has a relatively high heritability of 50%-80%. BMD is a complex trait determined by multiple genes, and BMD has been counted as one of the best surrogate phenotypes for osteoporosis genetics studies. Emerging as a central factor in the regulation of calcium metabolism, Calcium Sensing Receptor (CASR) is an important factor in the control of bone and mineral metabolism in general. Inconsistent results have been achieved in the association or linkage studies of the relationship between the CASR gene A986S polymorphism and BMD variation in different populations. Our study was designed to simultaneously investigate association and/or linkage of a cytosine-adenine (CA) repeat polymorphism in the CASR gene with BMD variation in a sample of 1, 263 subjects from 402 Chinese nuclear families at the same time. Each family consists of both parents and at least one daughter aged between 20-45 years. BMD (g/cm2) and bone area were measured at the lumbar spine and hip using dual-energy X-ray absorptiometry (DXA). Employing the QTDT (quantitative transmission disequilibrium tests) program, we find significant total association (p = 0.0066) and marginally significant within-family association (p = 0. 0756) between the CASR Al allele with BMD at the femoral neck, and significant total association (p - 0.02) between the CASR A6 allele with femoral neck BMD. Our results suggest that the CASR gene may have influence on the variation of hip BMD in...