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Titolo:
Two newly identified SNPs in the APO AI-CIII intergenic region are strongly associated with familial combined hyperlipidaemia
Autore:
Groenendijk, M; Cantor, RM; Funke, H; Dallinga-Thie, GM;
Indirizzi:
Univ Med Ctr Utrecht, Dept Internal Med, NL-3508 GA Utrecht, Netherlands Univ Med Ctr Utrecht Utrecht Netherlands NL-3508 GA Utrecht, Netherlands Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA Univ Calif Los Angeles Los Angeles CA USA man Genet, Los Angeles, CA USA Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA Univ Calif Los Angeles Los Angeles CA USA 90024 Los Angeles, CA 90024 USA Univ Munster, Div Med Genet, D-4400 Munster, Germany Univ Munster Munster Germany D-4400 v Med Genet, D-4400 Munster, Germany
Titolo Testata:
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
fascicolo: 10, volume: 31, anno: 2001,
pagine: 852 - 859
SICI:
0014-2972(2001)31:10<852:TNISIT>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
APOLIPOPROTEIN-C-III; IV GENE-CLUSTER; ATHEROGENIC LIPOPROTEIN PHENOTYPE; FRAGMENT-LENGTH-POLYMORPHISMS; INSULIN-RESPONSE ELEMENT; CORONARY-ARTERY DISEASE; HEART-DISEASE; LIPASE GENE; B LEVELS; HYPERTRIGLYCERIDEMIA;
Keywords:
apolipoprotein CIII; familial combined hyperlipidaemia; lipids; lipoproteins;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Dallinga-Thie, GM Univ Med Ctr Utrecht, Dept Internal Med, G02-228,POB 85500, NL-3508 GA Utrecht, Netherlands Univ Med Ctr Utrecht G02-228,POB 85500 Utrecht Netherlands NL-3508 GA
Citazione:
M. Groenendijk et al., "Two newly identified SNPs in the APO AI-CIII intergenic region are strongly associated with familial combined hyperlipidaemia", EUR J CL IN, 31(10), 2001, pp. 852-859

Abstract

Background We previously reported linkage and association of the apoAI-CIII-AIV gene region on chromosome 11 with familial combined hyperlipidaemia (FCHL). However, the observed epistasis resulting in an increased susceptibility to FCHL still remains unexplained. We hypothesize that the region between the apo AI and apo CIII genes may harbour functional mutations that might be in linkage disequilibrium with the already identified SstI and MspI polymorphisms, and provide an alternative explanation for the observed relationship. Methods Using sequence analysis, we identified four new single nucleotide polymorphisms (SNPs) in the apo AI-CIII intergenic region. These four variants, T3213C, A(3235)C, T3287C and A(5132)C, were studied in 30 FCHL probands, 159 hyperlipidaemic relatives, 327 normolipidaemic relatives, and 218 spouses from the same families in which the original results were obtained. Results The allele frequencies were significantly different between probands and spouses (P < 0.05). Transmission/disequilibrium test (TDT) analyses revealed more frequent transmission of the minor alleles to the affected offspring. The minor genotype was associated with elevated plasma cholesteroland triglyceride levels. The T3213C and MspI, and the A(3235)C and SstI SNPs were in complete linkage disequilibrium, resulting in two different major haplotypes 2-2-1-2-2-1 and 1-1-2-2-2-2 (MspI-T3213C-A(3235)C-T3287C-A(5132)C-SstI). Both haplotypes appear to predispose to FCHL independently, and account, together with the wild-type, for almost 90% of those occurring in these FCHL families, extending the high-risk combination of haplotypes thatwere reported previously. Conclusion These newly identified additional intergenic SNPs therefore provide an alternative explanation for the observed association of the SstI and MspI polymorphisms to the increased susceptibility for FCHL.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/01/20 alle ore 21:59:34