No Evidence for Linkage and/or Association of Human Alpha2-HS Glycoprotein Gene with Bone Mineral Density Variation in Chinese Nuclear Families

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.

Contribution of Myostatin gene polymorphisms to normal variation in lean mass, fat mass and peak BMD in Chinese male offspring

“…Our sample size in this study is in line with the sample size of the female-offspring nuclear families in our previous study. The latter has more than 80% power to test a candidate gene as a quantitative trait loci (QTL) and can explain about 10% of the bone phenotype variation [1,13,18,19] . Using the female-offspring nuclear families, we not only detected an association between Myostatin polymorphisms and BMD variation, but we also successfully observed that genetic polymorphisms in estrogen receptor α and collagen1α2 likely influenced the attainment of peak BMD in Chinese females [1,18,20] .…”

Polymorphisms in the HOXD4 gene are not associated with peak bone mineral density in Chinese nuclear families

“…We excluded 15 individuals whose DNA could not be amplified to discriminate genotype due to its poor quality, and 6 daughters who deviated from Mendelian inheritance. As previously reported, we ultimately acquired 401 integrated female-offspring nuclear families comprising 1260 individuals [7,[16][17][18] . The average family size was 3.14; 348 families had one child, 50 families had two children, 2 families had three children, and 1 family had four children.…”

“…The average family size was 3.14; 348 families had one child, 50 families had two children, 2 families had three children, and 1 family had four children. Exclusion criteria were adopted as previously reported [7,[16][17][18] .…”

“…Until now, no study has reported an association between single nucleotide polymorphisms (SNPs) of the HOXD4 gene and BMD in humans. The majority of the association studies between genotypes and BMD have been performed in women [7,[16][17][18][19][20] . Therefore, we recruited two cohorts of nuclear families where one cohort contained only male offspring and the other cohort contained only female offspring.…”

Association between SNP and haplotypes in PPARGC1 and adiponectin genes and bone mineral density in Chinese nuclear families

“…The recruiting daughters were healthy. The exclusion criteria was adopted as previously reported [17,18] . BMD measurements BMD (g/cm 2 ) of the anteroposterior lumber spine 1-4 (L1-4) and left proximal femur including total hip and femoral neck were measured by dual-energy X-ray absorptiometry (DXA) on a Hologic QDR 2000 (Hologic Inc, Bedford, MA, USA).…”