000168744 001__ 168744
000168744 005__ 20260218132343.0
000168744 0247_ $$2doi$$a10.1016/S0140-6736(97)09490-7
000168744 0248_ $$2sideral$$a1293
000168744 037__ $$aART-1998-1293
000168744 041__ $$aeng
000168744 100__ $$0(orcid)0000-0001-8807-9187$$aPocovi, Miguel$$uUniversidad de Zaragoza
000168744 245__ $$aß-glucocerebrosidase gene locus as a link for Gaucher's disease and familial hypo-a-lipoproteinaemia
000168744 260__ $$c1998
000168744 5060_ $$aAccess copy available to the general public$$fUnrestricted
000168744 5203_ $$aBackground. Gaucher''s disease is the most common lysosomal storage disorder, caused by deficiency of glucocerebrosidase resulting from homozygosity for any of several mutations of the glucocerebrosidase gene locus. Affected people have decreased concentrations of LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C). We assessed the association between mutations in the glucocerebrosidase locus and hypo-α-lipoproteinaemia. Methods. We studied 258 people from 43 unrelated Spanish families. 57 participants were affected, 137 were non-affected carriers, and 64 were non-carriers. We determined glucocerebrosidase genotypes and measured plasmid lipids, apolipoproteins A-I, B, and E, and leucocyte glucocerebrosidase activity. Findings. The most common glucocerebrosidase mutations were N370S (45%), L444P (23%), and G377S (5%). Deletions and recombinants accounted for another 5%, and point mutations in exons 5, 6, 9, and 10 were present in 12%. Affected participants had lower LDL-C and HDL-C concentrations than non-affected carriers (p < 0.001) and non-carriers (p < 0.001). HDL-C values were also significantly different between the non-affected carriers and non-carriers. Mutations at this locus may account for as much as 19.5% of the genetic variability in HDL-C in the population studied. Interpretation. Heterozygosity for these mutations at the glucocerebrosidase locus does not result in clinical expression of Gaucher''s disease but can decrease HDL-C concentrations. Given the high frequency of these mutations, the glucocerebrosidase locus might lead to familiar low α-lipoproteinaemia in up to 2% of the general population and be one of the most common known genetic causes of HDL-C.
000168744 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
000168744 590__ $$a11.793$$b1998
000168744 591__ $$aMEDICINE, GENERAL & INTERNAL$$b2 / 106 = 0.019$$c1998$$dQ1$$eT1
000168744 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000168744 700__ $$aCenarro, Ana
000168744 700__ $$0(orcid)0000-0001-7043-0952$$aCiveira, Fernando$$uUniversidad de Zaragoza
000168744 700__ $$0(orcid)0000-0001-9760-1248$$aTorralba, Miguel A
000168744 700__ $$0(orcid)0000-0003-2361-9941$$aPerez-Calvo, Juan I$$uUniversidad de Zaragoza
000168744 700__ $$0(orcid)0000-0001-5956-4319$$aMozas, Pilar
000168744 700__ $$0(orcid)0000-0002-8791-1901$$aGiraldo, Pilar
000168744 700__ $$aGiralt, Manuel
000168744 700__ $$aMyers, Richard H
000168744 700__ $$aCupples, L Adrienne
000168744 700__ $$aOrdovas, Jose M
000168744 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina y Psiquiatr.$$cArea Medicina
000168744 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000168744 773__ $$g351, 9120 (1998), 1919-1923$$pLancet$$tThe Lancet$$x0140-6736
000168744 8564_ $$s268788$$uhttps://zaguan.unizar.es/record/168744/files/texto_completo.pdf$$yPostprint
000168744 8564_ $$s2205589$$uhttps://zaguan.unizar.es/record/168744/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000168744 909CO $$ooai:zaguan.unizar.es:168744$$particulos$$pdriver
000168744 951__ $$a2026-02-18-12:27:33
000168744 980__ $$aARTICLE