Article

Calcified Tissue International

, Volume 87, Issue 1, pp 14-24

First online:

Analysis of Three Functional Polymorphisms in Relation to Osteoporosis Phenotypes: Replication in a Spanish Cohort

  • Lídia AguedaAffiliated withDepartment of Genetics, Faculty of Biology, University of BarcelonaInstitut de Biomedicina de la Universitat de Barcelona (IBUB)CIBER de Enfermedades Raras (CIBERER)
  • , Roser UrreiztiAffiliated withDepartment of Genetics, Faculty of Biology, University of BarcelonaInstitut de Biomedicina de la Universitat de Barcelona (IBUB)CIBER de Enfermedades Raras (CIBERER)
  • , Mariona BustamanteAffiliated withDepartment of Genetics, Faculty of Biology, University of BarcelonaInstitut de Biomedicina de la Universitat de Barcelona (IBUB)CIBER de Enfermedades Raras (CIBERER)
  • , Susana JuradoAffiliated withInternal Medicine, URFOA, IMIM, Hospital del Mar, Autonomous University of BarcelonaRed Temática de Investigación Cooperativa en Envejecimiento y Fragilidad (RETICEF)
  • , Natàlia Garcia-GiraltAffiliated withInternal Medicine, URFOA, IMIM, Hospital del Mar, Autonomous University of BarcelonaRed Temática de Investigación Cooperativa en Envejecimiento y Fragilidad (RETICEF)
  • , Adolfo Díez-PérezAffiliated withInternal Medicine, URFOA, IMIM, Hospital del Mar, Autonomous University of BarcelonaRed Temática de Investigación Cooperativa en Envejecimiento y Fragilidad (RETICEF)
  • , Xavier NoguésAffiliated withInternal Medicine, URFOA, IMIM, Hospital del Mar, Autonomous University of BarcelonaRed Temática de Investigación Cooperativa en Envejecimiento y Fragilidad (RETICEF)
  • , Leonardo MellibovskyAffiliated withInternal Medicine, URFOA, IMIM, Hospital del Mar, Autonomous University of BarcelonaRed Temática de Investigación Cooperativa en Envejecimiento y Fragilidad (RETICEF)
  • , Daniel GrinbergAffiliated withDepartment of Genetics, Faculty of Biology, University of BarcelonaInstitut de Biomedicina de la Universitat de Barcelona (IBUB)CIBER de Enfermedades Raras (CIBERER)
    • , Susana BalcellsAffiliated withDepartment of Genetics, Faculty of Biology, University of BarcelonaInstitut de Biomedicina de la Universitat de Barcelona (IBUB)CIBER de Enfermedades Raras (CIBERER) Email author 

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Abstract

Osteoporosis is a complex disease involving many putative genetic factors. Association analysis of functional SNPs in candidate genes is an important tool for their identification. However, this approach is affected by limited power, population stratification, and other drawbacks that lead to discordant results. Replication in independent cohorts is essential. We performed association analyses of three functional polymorphisms previously associated with bone phenotypes—namely, Ala222Val in MTHFR, Ile1062Val in LRP6, and −13910C>T in LCT—in a cohort of 944 postmenopausal Spanish women, all of them with lumbar spine (LS) bone mineral density (BMD) data and most with femoral neck (FN) BMD and fracture data. We found significant differences between genotypes only for the MTHFR polymorphism and vertebral factures, with an OR of 2.27 (95% CI 1.17–4.38) for the TT vs. CC/CT genotypes, P = 0.018. We present genotype and allele frequency data for LCT −13910C>T for a Spanish population, where the T allele (conferring lactase persistence) has a frequency of 38.6%. Genotype frequencies were consistent with observed clines in Europe and with the prevalence of lactase nonpersistence. The LCT −13910C>T polymorphism was significantly associated with height and weight, such that T allele carriers were 0.88 cm taller (95% CI 0.08–1.59 cm, P = 0.032, adjusted by age) than CC individuals and TT homozygotes were 1.91 kg heavier than CC/CT individuals (95% CI 0.11–3.71 kg, P = 0.038, adjusted by age). In conclusion, no significant association was observed between the studied polymorphisms and LS BMD or FN BMD in postmenopausal Spanish women, and only MTHFR Ala222Val was associated with vertebral fractures.

Keywords

MTHFR LCT LRP6 Association study BMD Fracture