Skeletal strength, maintained through bone remodelling, is regulated through complex communication networks between bone cells and other tissues including endocrine cells. Bone also functions as an endocrine organ in its own right. The peptide hormone amylin (or Islet Amyloid Polypeptide (IAPP)), has links to both bone and energy metabolism. A member of the calcitonin family of peptides, it is co-secreted with insulin from pancreatic β-cells and is linked with diabetes-associated complications. As many diabetic patients are osteopenic, and amylin-deficient mice have low bone mineral density (BMD), variation in the IAPP gene may be hypothesised to play a role in the development of osteoporosis.
The objective of the study was to determine the association between single nucleotide polymorphisms (SNPs) in the IAPP gene on DXA measured BMD, quantitative ultrasound (QUS) of the calcaneous and incident fracture in the population based OPRA cohort of 75 year old women. Written informed consent was obtained from all participants. Four SNPs in IAPP, identified from HAPMAP were successfully genotyped by Taqman in 964 women. Statistical association with skeletal phenotypes was analysed (SPSS v22).
There was no association between IAPP SNPs and BMD at any skeletal site or QUS variables. Compared to women with the rs5484 SNP variant TT genotype, the risk of incident osteoporotic fracture was elevated in both CT and CC genotypes. However the association was not statistically significant (CT: OR 1.8 (CI: 0.983.5); P=0.058) (CC: HR 1.7 (CI: 0.943.2); P=0.080).
In conclusion, while the data does not support an association between the IAPP variants analysed and BMD or risk of fracture in this cohort, replication studies in larger sample sizes may be warranted to fully explore the contribution of genetic variation in IAPP to bone phenotypes at the population level.
14 May 2016 - 17 May 2016