RGD Reference Report - 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.

General

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.
Authors:	Wegner, L Andersen, G Sparso, T Grarup, N Glumer, C Borch-Johnsen, K Jorgensen, T Hansen, T Pedersen, O
Citation:	Wegner L, etal., Diabetes. 2007 Mar;56(3):694-8.
RGD ID:	1624985
Pubmed:	PMID:17327437 (View Abstract at PubMed)
DOI:	DOI:10.2337/db06-0927 (Journal Full-text)
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-naive 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.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
type 2 diabetes mellitus		IAGP		1624985	DNA:SNPs	RGD
type 2 diabetes mellitus		ISO	LMNA (Homo sapiens)	1624985; 1624985	DNA:SNPs	RGD

Objects Annotated

Genes (Rattus norvegicus)

Lmna (lamin A/C)

Genes (Mus musculus)

Lmna (lamin A)

Genes (Homo sapiens)

LMNA (lamin A/C)

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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.