|Cusano, Natalie E. -|
|Kiel, Douglas P. -|
|Demissie, Serkalem -|
|Karasik, David -|
|Cupples, L. Adrienne -|
|Corella, Dolores -|
|Gao, Qiong -|
|Yiannakouris, Nikos -|
|Ordovas, Jose M. -|
Submitted to: Calcified Tissue International
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 18, 2011
Publication Date: February 1, 2012
Citation: Cusano, N., Kiel, D., Demissie, S., Karasik, D., Cupples, L., Corella, D., Gao, Q., Richardson, K., Yiannakouris, N., Ordovas, J. 2012. A polymorphism in a gene encoding Perilipin 4 is associated with height but not with bone measures in individuals from the Framingham Osteoporosis Study. Calcified Tissue International. 90(2):96-197. Interpretive Summary: Osteoporosis is a skeletal disorder that may result in weakened bone or fracture risk. In the United States alone, 10% of adults aged 50 years or more suffer from osteoporosis, and the direct care expenditures for fractures from osteoporosis are estimated to be $12–$18 billion annually. Some researchers suggested that the genes that control fat formation are related to those involved in bone formation; others think that the genes are related to those responsible for bone mineral density. Our study shows that the genes related to height are important in bone regulation. So, the genes that influence human height may also affect bone disease.
Technical Abstract: There is increasing interest in identifying new pathways and candidate genes that confer susceptibility to osteoporosis. There is evidence that adipogenesis and osteogenesis may be related, including a common bone marrow progenitor cell for both adipocytes and osteoblasts. Perilipin 1 (PLIN1) and Perilipin 4 (PLIN4) are members of the PATS family of genes and are involved in lipolysis of intracellular lipid deposits. A previous study reported gender-specific associations between one polymorphism of PLIN1 and bone mineral density (BMD) in a Japanese population. We hypothesized that polymorphisms in PLIN1 and PLIN4 would be associated with bone measures in adult Caucasian participants of the Framingham Osteoporosis Study (FOS). We genotyped 1,206 male and 1,445 female participants of the FOS for four single-nucleotide polymorphism (SNPs) in PLIN1 and seven SNPs in PLIN4 and tested for associations with measures of BMD, bone ultrasound, hip geometry, and height. We found several gender-specific significant associations with the measured traits. The association of PLIN4 SNP rs8887, G>A with height in females trended toward significance after simulation testing (adjusted P = 0.07) and remained significant after simulation testing in the combined-sex model (adjusted P = 0.033). In a large study sample of men and women, we found a significant association between one SNP in PLIN4 and height but not with bone traits, suggesting that PATS family genes are not important in the regulation of bone. Identification of genes that influence human height may lead to a better understanding of the processes involved in growth and development.