title: 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.
abstract: 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 genotyped 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.
authors.affiliation: Steno Diabetes Center, Niels Steensens Vej 2, NSP1.03, DK-2820 Gentofte, Denmark. lwgn@steno.dk
authors.forename: Lise
authors.initials: L
authors.lastname: Wegner
authors.forename: Gitte
authors.initials: G
authors.lastname: Andersen
authors.forename: Thomas
authors.initials: T
authors.lastname: Sparsø
authors.forename: Niels
authors.initials: N
authors.lastname: Grarup
authors.forename: Charlotte
authors.initials: C
authors.lastname: Glümer
authors.forename: Knut
authors.initials: K
authors.lastname: Borch-Johnsen
authors.forename: Torben
authors.initials: T
authors.lastname: Jørgensen
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
mesh_terms: D000273:Adipose Tissue / Q000502:physiology*; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis / Q000235:genetics*; D001827:Body Height / Q000235:genetics*; D003718:Denmark; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005215:Fasting / Q000097:blood; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D044465:White People / Q000235:genetics*
chemical_list: D001786:Blood Glucose; C494847:LMNA protein, human; D034904:Lamin Type A