TY - JOUR

T1 - 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

T2 - studies of 7,495 Danish whites

AU - Wegner, Lise

AU - Andersen, Gitte

AU - Sparsø, Thomas

AU - Grarup, Niels

AU - Glümer, Charlotte

AU - Borch-Johnsen, Knut

AU - Jørgensen, Torben

AU - Hansen, Torben

AU - Pedersen, Oluf

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

KW - Adipose Tissue

KW - Adult

KW - Aged

KW - Blood Glucose

KW - Body Height

KW - Denmark

KW - Diabetes Mellitus, Type 2

KW - European Continental Ancestry Group

KW - Fasting

KW - Female

KW - Genetic Predisposition to Disease

KW - Genetic Variation

KW - Humans

KW - Lamin Type A

KW - Male

KW - Middle Aged

U2 - 10.2337/db06-0927

DO - 10.2337/db06-0927

M3 - Journal article

C2 - 17327437

VL - 56

SP - 694

EP - 698

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 3

ER -