Mutations in the <i>Lamin A/C</i> (<i>LMNA</i>) gene-encoding nuclear LMNA cause laminopathies, which include partial lipodystrophies associated with metabolic syndromes.
In this study, we hypothesized that MS may be, in some cases, a mild form of laminopathies and use the abnormal cell nucleus phenotype observed in these diseases as a primary screening test in patients suffering from common MS. Nuclear shape and lamin A nucleoplasmic distribution abnormalities were systematically searched in lymphoblastoid cells of 87 consecutive patients with MS.
Importantly, lamin A/Cmutations are also responsible for metabolic laminopathies, resembling the metabolic syndrome and progeria, a syndrome of premature aging.
We therefore investigated the effect of single nucleotide polymorphisms (SNPs) in the LMNA gene in combination with four other genes encoding enzymes influencing lamin post-translational maturation on risk of metabolic syndrome (MS).
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.
For instance, evaluation of the clinical features of carriers of mutant LMNA in kindreds with familial partial lipodystrophy suggests rational, staged intervention using established pharmaceutical agents to prevent cardiovascular complications not just for patients with lipodystrophy but by extension for patients with the common metabolic syndrome.
LMNA maps to the well-replicated diabetes-linkage region on chromosome 1q, and there are reported associations between LMNA single nucleotide polymorphisms (SNPs) (particularly rs4641; H566H) and metabolic syndrome components.
Although adipokines have been implicated, few data exist in subjects with FPLD; therefore we investigated a family with FPLD due to a lamin A/C mutation in order to determine how abnormalities of the plasma adipokine profile relate to insulin resistance and the metabolic syndrome.