Jai Prakash1, Maria Herlin1,2, Jitender Kumar3, Gaurav Garg4, Kristina E Akesson1,5, Peter S Grabowski6, Tim M Skerry7, Gareth O Richards7, Fiona E A McGuigan1. 1. Lund University, Dept. of Clinical Sciences Malmö, Clinical and Molecular Osteoporosis Research Unit, Sweden. 2. Dept. of Environmental Research and Monitoring, Swedish Museum of Natural History, Stockholm, Sweden. 3. Amity Institute of Biotechnology, Amity University Uttar Pradesh, Noida, India. 4. Genomics Division, LCGC Life sciences LLP, New Delhi, India. 5. Skåne University Hospital, Dept. of Orthopedics, Malmö, Sweden. 6. Human Nutrition Unit, Dept. of Oncology and Metabolism, Sheffield University, UK. 7. Academic Unit of Bone Biology, Dept. of Oncology and Metabolism, Sheffield University, UK.
Abstract
BACKGROUND AND AIM: The Receptor Activity Modifying Proteins (RAMPs) are a group of accessory proteins, of which there are three in humans, that interact with a number of G-protein coupled receptors (GPCR) and play various roles in regulation of endocrine signaling. Studies in RAMP3 knockout (KO) mice reveal an age related phenotype with altered metabolic regulation and high bone mass. To translate these findings into a clinically relevant perspective, we investigated the association between RAMP3 gene variants, body composition and bone phenotypes in two population-based cohorts of Swedish women. METHODS: Five single nucleotide polymorphisms (SNP) in the vicinity of the RAMP3 gene were genotyped in the PEAK-25 cohort (n = 1061; 25 years) and OPRA (n = 1044; 75 years). Bone mineral density (BMD), fat mass and lean mass (total body; regional) were measured by DXA at baseline, 5 and 10 year follow-up. RESULTS: BMD did not differ with RAMP3 genotype in either cohort, although fracture risk was increased in the elderly women (OR 2.695 [95% CI 1.514-4.801]). Fat mass tended to be higher with RAMP3 SNPs; although only in elderly women. In the young women, changes in BMI and fat mass between ages 25-35 differed by genotype (p = 0.001; p < 0.001). CONCLUSION: Variation in RAMP3 may contribute to age-related changes in body composition and risk of fracture.
BACKGROUND AND AIM: The Receptor Activity Modifying Proteins (RAMPs) are a group of accessory proteins, of which there are three in humans, that interact with a number of G-protein coupled receptors (GPCR) and play various roles in regulation of endocrine signaling. Studies in RAMP3 knockout (KO) mice reveal an age related phenotype with altered metabolic regulation and high bone mass. To translate these findings into a clinically relevant perspective, we investigated the association between RAMP3 gene variants, body composition and bone phenotypes in two population-based cohorts of Swedish women. METHODS: Five single nucleotide polymorphisms (SNP) in the vicinity of the RAMP3 gene were genotyped in the PEAK-25 cohort (n = 1061; 25 years) and OPRA (n = 1044; 75 years). Bone mineral density (BMD), fat mass and lean mass (total body; regional) were measured by DXA at baseline, 5 and 10 year follow-up. RESULTS: BMD did not differ with RAMP3 genotype in either cohort, although fracture risk was increased in the elderly women (OR 2.695 [95% CI 1.514-4.801]). Fat mass tended to be higher with RAMP3 SNPs; although only in elderly women. In the young women, changes in BMI and fat mass between ages 25-35 differed by genotype (p = 0.001; p < 0.001). CONCLUSION: Variation in RAMP3 may contribute to age-related changes in body composition and risk of fracture.
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Authors: Paris Avgoustou; Ameera B A Jailani; Jean-Olivier Zirimwabagabo; Matthew J Tozer; Karl R Gibson; Paul A Glossop; James E J Mills; Roderick A Porter; Paul Blaney; Peter J Bungay; Ning Wang; Alice P Shaw; Kamilla J A Bigos; Joseph L Holmes; Jessica I Warrington; Timothy M Skerry; Joseph P A Harrity; Gareth O Richards Journal: ACS Pharmacol Transl Sci Date: 2020-06-25