Lamin A/C polymorphisms, type 2 diabetes, and the metabolic syndrome: case-control and quantitative trait studies.
Mutations in the LMNA gene, encoding the nuclear envelope protein lamin A/C, are responsible for a number of distinct disease entities including Dunnigan-type familial partial lipodystrophy. Dunningan-type lipodystrophy is characterized by loss of subcutaneous adipose tissue, insulin resistance, dyslipidemia, and type 2 diabetes and shares many of the features of the metabolic syndrome. Furthermore, several genome-wide linkage scans for type 2 diabetes have found evidence of linkage at chromosome 1q21.2, the region that harbors the LMNA gene. Therefore, LMNA is a biological and positional candidate for type 2 diabetes susceptibility. Previous studies have reported association between a common LMNA variant (1908C>T; rs4641) and adverse metabolic traits in ethnically diverse populations from Asia and North America. In the present study, we characterized the common variation across the LMNA gene (including rs4641) and tested for association with type 2 diabetes in two large case-control studies (n = 2,052) and with features of the metabolic syndrome in a separate cohort study (n = 1,572). Despite our study being sufficiently powered to detect effects similar and even smaller in magnitude than those previously reported, none of the LMNA single nucleotide polymorphisms were statistically significantly associated with type 2 diabetes or the metabolic syndrome. Thus, it appears unlikely that variation at LMNA substantially increases the risk of type 2 diabetes or related traits in U.K. Europids.
Mesa
José L
JL
Medical Research Center Epidemiology Unit, Cambridge, U.K.
Loos
Ruth J F
RJ
Franks
Paul W
PW
Ong
Ken K
KK
Luan
Jian'an
J
O'Rahilly
Stephen
S
Wareham
Nicholas J
NJ
Barroso
Inês
I
D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D015810:Linkage Disequilibrium; D024821:Metabolic Syndrome / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics*; D006113:United Kingdom
C494847:LMNA protein, human; D034904:Lamin Type A