on November 14, 2002
Published online before print November 14, 2002, doi: 10.1161/01.ATV.0000047460.27435.B8
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Submitted on September 19, 2002
Accepted on November 4, 2002
Elevated Serum C-Reactive Protein and Free Fatty Acids Among Nondiabetic Carriers of Missense Mutations in the Gene Encoding Lamin A/C (LMNA) With Partial Lipodystrophy
Robert A. Hegele *;
From the Blackburn Cardiovascular Genetics Laboratory and Vascular Biology Research Group, Robarts Research Institute, London, Ontario, Canada.
* To whom correspondence should be addressed. E-mail: robert.hegele{at}rri.on.ca.
Objective—Dunnigan-type familial partial lipodystrophy (FPLD) due to mutant LMNA is a monogenic form of insulin resistance. Affected subjects are at increased risk of early coronary heart disease (CHD), especially women. Although common insulin resistance is associated with several biochemical perturbations, including elevated C-reactive protein (CRP), the biochemical profile in subjects with mutant LMNA is incompletely defined.
Methods and Results—We studied 35 nondiabetic adult FPLD subjects (of whom 24 were women) with either the LMNA R482Q or R482W missense mutations and 51 matched normal first-degree relatives (of whom 27 were women). Compared with normal controls, LMNA mutation carriers had significantly higher plasma insulin and more dyslipidemia, higher mean triglycerides and lower HDL cholesterol, significantly higher nonesterified free fatty acids and CRP, and significantly lower leptin and adiponectin than controls. Subgroup analyses showed that these differences were more pronounced in women. Other biomarkers such as resistin, fibrinogen, and plasminogen activator inhibitor-1 were not different between groups.
Conclusions—LMNA mutations in nondiabetic patients with FPLD are associated with several metabolic and biochemical changes, particularly in women. The unfavorable profile might contribute to the increased susceptibility to CHD seen in LMNA mutation carriers.
Key words: insulin resistance • diabetes • DNA analysis • cytokines • risk factor
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