No abstract

No abstract

Osteoporosis is an important health problem in the world. Alpha2-HS glycoprotein (AHSG) is involved in bone formation and metabolism and has been considered as an important candidate gene for osteoporosis. In this study, we simultaneously tested linkage and/or association of the AHSG gene with the variation of bone mineral density (BMD), an important risk factor for osteoporosis. A sample of 1,260 subjects from 401 Chinese nuclear families (including both parents and their daughters) were studied. The daughters' ages ranged from 20 to 45 years. All the subjects were genotyped by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) at polymorphic Sac I site inside the exon 7 of the AHSG gene. This polymorphism involves a nucleotide substitution of C to G at the middle nucleotide of the codon at amino acid position 238, resulting in the replacement of threonine (ACC) with serine (AGC). BMD was measured at the lumbar spine and hip region by dual-energy X-ray absorptiometry (DXA). Using the QTDT (quantitative trait transmission disequilibrium test), we found no significant results for association or linkage between the AHSG gene and BMD variation at the spine or hip. Our data provided no evidence to support the AHSG gene as a quantitative trait locus (QTL) for the BMD variation in a Chinese population.

Low bone mineral density (BMD) is a major risk factor for osteoporotic fracture. To identify genomic regions harboring quantitative trait loci (QTLs) contributing to BMD variation, we performed a two-stage genome screen. The first stage involved genotyping of a sample of 53 pedigrees with 630 individuals using 400 microsatellite markers spaced at approximately 10-cM intervals throughout the genome. Ten genomic regions with multi- and/or two-point LOD scores greater than 1.5 were observed. In the present second-stage study, 60 microsatellite markers, with a mean spacing of about 5 cM, were genotyped in these regions in an expanded sample of 79 pedigrees that contained 1816 subjects. Each pedigree was ascertained through a proband with extreme BMD at the hip or spine. BMD at the spine (L1-4), hip (the femoral neck, trochanter, and intertrochanteric region), and wrist (the ultradistal region) was measured by dual-energy X-ray absorptiometry (DXA) and was adjusted for age, sex, height, and weight. Two-point and multipoint linkage analyses were performed for each BMD site using statistical genetic methods that are implemented in the computer package SOLAR. Several regions (7q11, 10q26, 12q13, and 12q24) achieved LOD scores in excess of 1 in the second-stage followup study. The current results replicate some of our previous linkage findings and also highlight some of the difficulties facing microsatellite linkage mapping for complex human diseases.

No abstract