A patient with Werner syndrome and adiponectin gene mutation.

Werner syndrome is a premature aging disease characterized by genomic instability and increased cancer risk. Here, we report a 45-year-old diabetic man as the first Werner syndrome patient found to have an adiponectin gene mutation. Showing graying and loss of hair, skin atrophy, and juvenile cataract, he was diagnosed with Werner syndrome type 4 by molecular analysis. His serum adiponectin concentration was low. In the globular domain of the adiponectin gene, I164T in exon 3 was detected. When we examined effects of pioglitazone (15 mg/day) on serum adiponectin multimer and monomer concentrations using selective assays, the patient's relative percentage increased in adiponectin concentration was almost same as that in the 18 diabetic patients without an adiponectin mutation, but the absolute adiponectin concentration was half of those seen in diabetic patients treated with the same pioglitazone dose who had no adiponectin mutation. The response suggested that pioglitazone treatment might help to prevent future Werner syndrome-related acceleration of atherosclerosis. Present and further clinical relevant to atherosclerosis in this patient should be imformative concerning the pathogenesis and treatment of atherosclerosis in the presence of hypoadiponectinemia and insulin resistance.

Association of hypoadiponectinemia in men with early onset of coronary heart disease and multiple coronary artery stenoses.

Adiponectin influences insulin sensitivity and lipid oxidation. Because low plasma adiponectin concentrations are suspected to promote atherosclerosis, we retrospectively assessed relationships of plasma adiponectin concentration to characteristics of coronary heart disease (CHD). Japanese men undergoing coronary angiography for CHD (n = 139) were grouped according to serum adiponectin concentration by enzyme-linked immunosorbent assay (low, <4.0; medium, 4.0-8; high, >8.0 microg/mL). Numbers of coronary arteries with at least 50% stenosis were determined. Serum adiponectin concentration correlated positively with age at onset of CHD (r = 0.285, P = .003). Age at CHD onset in the low-adiponectin group was younger than in the medium or high groups. Adiponectin was protective against CHD onset at ages younger than 58 years (relative risk, 0.778; P = .0047). Significantly more arteries were affected in low-adiponectin patients than in the medium or high group (each P < .01). Adiponectin concentration correlated positively with high-density lipoprotein cholesterol concentration and negatively with triglyceride concentration. Only in diabetic patients did serum adiponectin concentration correlate negatively with body mass index. Low plasma adiponectin concentrations were associated with early CHD onset and multiple atherosclerotic lesions in coronary arteries. Thus, adiponectin concentrations may influence risk of CHD and might serve as one of the screening tests facilitating early intervention.