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.
Keywords:
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.