PMID- 15205219
OWN - NLM
STAT- MEDLINE
DCOM- 20050405
LR  - 20211203
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 24
IP  - 9
DP  - 2004 Sep
TI  - Variation in the lamin A/C gene: associations with metabolic syndrome.
PG  - 1708-13
AB  - OBJECTIVE: Metabolic syndrome is associated with increased risk for 
      cardiovascular disease and type 2 diabetes mellitus (T2DM). The lamin A/C (LMNA) 
      gene, mutations of which cause rare syndromes of severe insulin resistance and 
      dyslipidemia, is located on chromosome 1q21-q24, a region linked to T2DM in 
      several genome wide scans, including in the Old Order Amish. To determine whether 
      polymorphisms in LMNA influence susceptibility to metabolic syndrome and its 
      constituent components. METHODS AND RESULTS: We performed DNA sequence analysis 
      of LMNA. Six single-nucleotide polymorphisms (SNPs) were identified: c.141889C>T 
      (intron 3), c.141906G>T (intron 3), A287A (c.141253T>C; exon 5), c.140353G>A 
      (intron 6), c.139418C>T (intron 8), and H566H (c. 138747C>T; exon 10). In 971 
      participants from the Amish Family Diabetes Study, the H566H polymorphism of LMNA 
      was associated with metabolic syndrome diagnosed according to National 
      Cholesterol Education Program ATP III criteria and also higher mean fasting 
      triglyceride and lower mean high-density lipoprotein-cholesterol concentrations. 
      However, no differences in allele frequencies were observed for any SNP among 
      participants with T2DM or impaired glucose homeostasis (IGH) and normoglycemic 
      controls. Haplotype analysis showed that >87% of individuals carried 1 of 2 
      common LMNA haplotypes. There were no significant differences in haplotype 
      frequencies among subjects with metabolic syndrome T2DM, IGH, and controls. 
      CONCLUSIONS: Sequence variation in LMNA may confer modest susceptibility for 
      development of metabolic syndrome and dyslipidemia in the Amish. To determine 
      whether polymorphisms in LMNA influence susceptibility to metabolic syndrome and 
      its constituent components, we performed DNA analysis of polymorphisms in LMNA. 
      The H566H polymorphism was associated with metabolic syndrome and also higher 
      mean fasting triglyceride and lower mean HDL-cholesterol concentrations in the 
      Old Order Amish.
FAU - Steinle, Nanette I
AU  - Steinle NI
AD  - Department of Medicine, University of Maryland School of Medicine, Baltimore 
      21201, USA. nsteinle@medicine.umaryland.edu
FAU - Kazlauskaite, Rasa
AU  - Kazlauskaite R
FAU - Imumorin, Ikhide G
AU  - Imumorin IG
FAU - Hsueh, Wen-Chi
AU  - Hsueh WC
FAU - Pollin, Toni I
AU  - Pollin TI
FAU - O'Connell, Jeffrey R
AU  - O'Connell JR
FAU - Mitchell, Braxton D
AU  - Mitchell BD
FAU - Shuldiner, Alan R
AU  - Shuldiner AR
LA  - eng
GR  - K24 DK02673/DK/NIDDK NIH HHS/United States
GR  - R01 DK 54261/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040617
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Lamin Type A)
RN  - 0 (Lipoproteins, HDL)
RN  - 0 (lamin C)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Alleles
MH  - Chromosomes, Human, Pair 1/genetics
MH  - Cohort Studies
MH  - Consanguinity
MH  - Diabetes Mellitus, Type 2/genetics
MH  - Ethnicity/*genetics
MH  - Exons/genetics
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Haplotypes/genetics
MH  - Humans
MH  - Hyperglycemia/genetics
MH  - Hyperinsulinism/genetics
MH  - Hypertriglyceridemia/genetics
MH  - Insulin Resistance/genetics
MH  - Lamin Type A/*genetics/physiology
MH  - Linkage Disequilibrium
MH  - Lipoproteins, HDL/blood
MH  - Male
MH  - Metabolic Syndrome/*genetics
MH  - Middle Aged
MH  - Obesity/genetics
MH  - Pennsylvania
MH  - *Polymorphism, Single Nucleotide
EDAT- 2004/06/19 05:00
MHDA- 2005/04/06 09:00
CRDT- 2004/06/19 05:00
PHST- 2004/06/19 05:00 [pubmed]
PHST- 2005/04/06 09:00 [medline]
PHST- 2004/06/19 05:00 [entrez]
AID - 01.ATV.0000136384.53705.c9 [pii]
AID - 10.1161/01.ATV.0000136384.53705.c9 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2004 Sep;24(9):1708-13. doi: 
      10.1161/01.ATV.0000136384.53705.c9. Epub 2004 Jun 17.