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

Abstract

Aim: To assess the contribution of single nucleotide polymorphisms (SNP) and haplotypes in the peroxisome proliferator-activated receptor-γ co-activator-1 (PPARGC1) and adiponectin genes to normal bone mineral density (BMD) variation in healthy Chinese women and men. Methods: We performed populationbased (ANOVA) and family-based (quantitative trait locus transmission disequilibrium test) association studies of PPARGC1 and adiponectin genes. SNP in the 2 genes were genotyped. BMD was measured using dual-energy X-ray absorptiometry in the lumbar spine and hip in 401 nuclear families with a total of 1260 subjects, including 458 premenopausal women, 20-40 years of age; 401 postmenopausal women (mothers), 43-74 years of age; and 401 men (fathers), 49-76 years of age. Results: Significant within-family association was found between the Thr394Thr polymorphism in the PPGAGC1 gene and peak BMD in the femoral neck (P=0.026). Subsequent permutations were in agreement with this significant within-family association result (P=0.016), but Thr394Thr SNP only accounted for 0.7% of the variation in femoral neck peak BMD. However, no significant withinfamily association was detected between each SNP in the adiponectin gene and peak BMD. Although no significant association was found between BMD and SNP in the PPARGC1 and adiponectin genes in both men and postmenopausal women, haplotype 2 (T-T) in the adiponectin gene was associated with lumbar spine BMD in postmenopausal women (P=0.019). Conclusion: Our findings suggest that Thr394Thr SNP in the PPARGC1 gene was associated with peak BMD in the femoral neck in Chinese women. Confirmation of our results is needed in other populations and with more functional markers within and flanking the PPARGC1 or adiponectin genes region.

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.…”

“…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.…”

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

“…The coefficient of variability (CV) values were obtained from 15 volunteers with 3 measurements each. The respective CV values for the BMD of the lumbar spine 1-4, total hip, femoral neck, and trochanter were 1.39%, 0.70%, 2.22%, and 1.41% [1,[13][14][15] . The respective CV values for the fat mass measurements at the upper limbs, lower limbs, trunk, and total body were 7.58%, 3.28%, 2.52%, and 3.72%; the CV values for the lean mass at these sites were 1.18%, 1.59%, 1.12%, and 1.18%, respectively [15] .…”

“…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] .…”

Association of ALOX15 gene polymorphisms with obesity-related phenotypes in Chinese nuclear families with male offspring

“…However, raw obesity phenotypic measurements, such as BMI, TFM, tFM, AFM, LFM, and percentage of fat mass (PFM), which are covariates, were adjusted by age. Because false-positive results can confound conclusions, the reliability of our results was assessed by performing a permutation procedure (1000 simulations) to generate empirical P values [22,23] . The statistical power was estimated with Piface (version 1.65) (http://www.math.uiowa.edu/~rlenth/ Power/) taking into account the sample size, minor allele frequency of every genotype and variation in obesity phenotypes.…”