Common variation in LMNA increases susceptibility to type 2 diabetes and associates with elevated fasting glycemia and estimates of body fat and height in the general population: Studies of 7,495 Danish whites

Lise Wegner, Gitte Andersen, Thomas Sparsø, Niels Grarup, Charlotte Glümer, Knut Borch-Johnsen, Torben Jørgensen, Torben Hansen, Oluf Pedersen

    Publikation: Bidrag til tidsskriftArtikelForskningpeer review

    Abstrakt

    Mutations in LMNA encoding lamin A and C proteins cause monogenic syndromes characterized by muscular dystrophy and familial partial lipodystrophy. Eight tag single nucleotide polymorphisms in the LMNA locus were geno-typed in 7,495 Danish whites and related to metabolic and anthropometric traits. The minor T-allele of rs4641 was nominally associated with type 2 diabetes (odds ratio 1.14 [95% CI 1.03-1.26], P = 0.01) in a study of 1,324 type 2 diabetic patients and 4,386 glucose-tolerant subjects and with elevated fasting plasma glucose levels in a population-based study of 5,395 middle-aged individuals (P = 0.008). The minor T-allele of rs955383 showed nominal association with obesity in a study of 5,693 treatment-naïve subjects (1.25 [1.07-1.64], P = 0.01), and after dichotomization of waist circumference, the minor alleles of rs955383 and rs11578696 were nominally associated with increased waist circumference (1.14 [1.04 -1.23], P = 0.003; 1.12 [1.00 -1.25], P = 0.04). The minor G-allele of rs577492 was associated with elevated fasting serum cholesterol and short stature (P = 3.0 = 10-5 and P = 7.0 = 10-4). The findings are not corrected for multiple comparisons and are by nature exploratory. However, if replicated, these findings suggest that less severe variation in a gene locus known to harbor severe mutations causing monogenic syndromes may modestly increase susceptibility to common metabolic and anthropometrical phenotypes of polygenic origin.

    OriginalsprogEngelsk
    Sider (fra-til)694-698
    Antal sider5
    TidsskriftDiabetes
    Vol/bind56
    Udgave nummer3
    DOI
    StatusUdgivet - 1 mar. 2007

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    Udforsk hvilke forskningsemner 'Common variation in LMNA increases susceptibility to type 2 diabetes and associates with elevated fasting glycemia and estimates of body fat and height in the general population: Studies of 7,495 Danish whites' indeholder.

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