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USF1 gene variants contribute to metabolic traits in men in a longitudinal 32-year follow-up study
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. (Diabetes och endokrinologi)
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2008 (engelsk)Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 51, nr 3, s. 464-472Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

AIMS/HYPOTHESIS:

Genetic variants of upstream transcription factor 1 (USF1) have previously been associated with dyslipidaemias in family studies. Our aim was to further address the role of USF1 in metabolic syndrome and cardiovascular traits at the population level in a large Swedish male cohort (n=2,322) with multiple measurements for risk factors during 32 years of follow-up.

METHODS:

Participants, born in 1920-1924, were examined at 50, 60, 70 and 77 years of age. The follow-up period for cardiovascular events was 1970-2002. We genotyped three haplotype tagging polymorphisms capturing the major allelic variants of USF1.

RESULTS:

SNP rs2774279 was associated with the metabolic syndrome. The minor allele of rs2774279 was less common among individuals with metabolic syndrome than among healthy controls [p=0.0029 when metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III; p=0.0073 when defined according to the International Diabetes Federation (IDF)]. The minor allele of rs2774279 was also associated with lower BMI, lower fasting glucose values and higher HDL-cholesterol concentrations in longitudinal analyses. With SNP rs2073658, a borderline association with metabolic syndrome was observed (p=0.036, IDF), the minor allele being the risk-increasing allele. The minor allele of rs2073658 also associated with higher total and LDL-cholesterol, apolipoprotein B-100 and lipoprotein(a) concentrations in longitudinal analyses. Importantly, these trends with respect to the allelic variants prevailed throughout the follow-up time of three decades.

CONCLUSIONS/INTERPRETATION:

Our results suggest that USF1 variants associate with the metabolic syndrome at population level and influence the cardiovascular risk factors throughout adulthood in a consistent, longitudinal manner.

sted, utgiver, år, opplag, sider
2008. Vol. 51, nr 3, s. 464-472
Emneord [en]
Cardiovascular diseases, Epidemiology, Genetics, Lipids, Metabolic syndrome, Syndrome X
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-106228DOI: 10.1007/s00125-007-0892-9ISI: 000252888200013PubMedID: 18097648OAI: oai:DiVA.org:uu-106228DiVA, id: diva2:224274
Tilgjengelig fra: 2009-06-17 Laget: 2009-06-17 Sist oppdatert: 2017-12-13bibliografisk kontrollert

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