1) Genetic basis of osteoporosis

Loss of bone mineral density (BMD) and defects in the microarchitecture of bone are the underlying cause of osteoporotic fracture. Twin and family studies indicate that genetic factors explain an important fraction of the variability in BMD. A cohort of 900 Spanish postmenopausal women was established. BMD values and DNA samples were collected from all the participants. The COL1A1 and CYP19 genes, encoding the ?1 subunit of type I collagen and the aromatase enzyme, respectively, were assayed as candidate genes for osteoporosis, both from a functional perspective and by means of association analyses. Other individual polymorphisms of classical candidates such as the VDR, ESR1 and TGF?, have also been studied within the European GENOMOS initiative. At present, we undertake the complete analysis of two genes (LRP5 and OPG) by genotyping all the relevant SNPs along their sequences and envisage the analysis of functional polymorphisms of a short-list of ten other candidates.



Staff
Dr. Daniel Grinberg
Dr. Susana Balcells


Erasmus student
Ulrik FanhØe


Technician
Mònica Cozar


Collaborators
Dr. Adolfo Díez-Pérez (Servei de Medicina Interna, Hospital del Mar)
Dr. Leonardo Mellivobski (Servei de Medicina Interna, Hospital del Mar)
Dr. Xavier Nogués Solan (Servei de Medicina Interna, Hospital del Mar)
Dr. Roberto Elosúa (Institut Municipal d'Investigacions Mèdiques)
Dr. Stuart Ralston (University of Edimburgh, UK)
Dr. André Uitterlinden (Erasmus University Rotterdam, Holanda)



2) Homocysteine and diesease: genetic aspects of homocystinuria and hyperhomocysteinemia
Homocysteine, a non-proteinogenic amino acid, is the product of methionine demethylation. Excess plasma homocysteine is associated with disease. Very high hyperhomocysteinaemia with homocystinuria is a rare autosomal recessive condition mainly due to defects in the CBS gene. We have analysed over 60 homocystinuric patients from Spain, Portugal, Argentina and Colombia for mutations in the CBS gene. A very prevalent mutation was identified, T191M, which accounts for over 50% of the mutant alleles. Its possible single origin is being investigated. Up to 6 other new mutations were identified and functional tests of their pathogenicity are being performed. Moderate hyperhomocysteinaemia, an independent risk factor for vascular disease, has a strong genetic component. Ten polymorphisms in five candidate genes (CBS, MTHFR, MTRR, MTR and GCPII) are being investigated for association to cardiovascular disease.

Staff
Dr. Susana Balcells
Dr. Daniel Grinberg

Postdocs
Carla Asteggiano

Predocs
Roser Urreizti Frexedas

Technician
Mònica Cozar

Collaborators
Dr. Mª Antònia Vilaseca (Hospital St. Joan de Déu, Esplugues de Llobregat, Barcelona)
Dr. Rafael Artuch (Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona)
Dr. Xavier Pintó (Unitat d'Arteriosclerosi, Centre Sanitari Universitari de Bellvitge, Barcelona)
Dr. Eva López Quesada (Hospital de Terrassa, Terrassa, Spain)
Dr. M. Rodés (Institut de Bioquímica Clínica, Barcelona)
Dr. L. Vilarinho (Porto, Portugal)
Dr. M.L. Couce (Santiago de Compostela, Spain)
Dr. Martha Bermúdez (Pontificia Universidad Javeriana, Bogotá, Colombia)
Dr. Alfonso Córdoba (Medellín, Colombia)
Dr. Raquel Kremer (Córdoba, Argentina)
Dr. Néstor Chamoles (Buenos Aires, Argentina)
Dr. Jan P. Kraus (University of Colorado, Denver, CO, USA)
Dr. Sílvia Atrian (Dept. Genètica, Universitat de Barcelona)