The Val81 missense mutation of the melanocortin 3 receptor gene, but not the 1908c/T nucleotide polymorphism in lamin A/C gene, is associated with hyperleptinemia and hyperinsulinemia in obese Greek caucasians.
FPLD was recently discovered to result from mutated LMNA (R482Q; OMIM #150330.0010), which is the gene encoding nuclear lamins A and C. Results from extended pedigrees indicate that dyslipidemia precedes the plasma glucose abnormalities in FPLD subjects with mutant LMNA, and that the hyperinsulinemia is present early in the course of the disease.
Through the use of focused DNA sequencing of positional candidate genes on chromosome 1q21, we discovered that FPLD results from mutations in LMNA (R482Q; OMIM 150330.0010), which is the gene that encodes nuclear lamins A and C. By stratifying members of extended FPLD pedigrees according to LMNA genotype, we found that hyperinsulinemia is present early in the course of the disease and that dyslipidemia (characterized by high triglycerides and depressed HDL cholesterol) precedes the development of glucose abnormalities.