A Promoter Polymorphism of Lamin A/C Gene is an Independent Genetic Predisposition to Arterial Stiffness in a Japanese General Population (The Tanno and Sobetsu Study)

Aim: We examined the hypothesis that there is a positive, independent association between polymorphisms of lamin A/C gene (LMNA) and arterial stiffness in Japanese. Methods: The subjects were 261 men (mean age, 64.4 +/- 0.7 years) selected from inhabitants of the towns of Tanno and Sobetsu in a rural area of Japan who underwent medical check-ups. We conducted clinical examinations, including measurement of bilateral brachial-ankle pulse wave velocity (baPWV) as a marker of arterial Stiffness, and genetic analysis. Subjects with atrial fibrillation, subjects with ankle-brachial index < 0.9, and subjects taking any medication were excluded. We selected two single nucleotide polymorphisms (SNPs) as markers of LMNA, 1908C/T in exon 10 and -1030C/T in the promoter region, which we have recently identified. All genotypes were clearly determined by the TaqMan PCR method. Results: Genotype frequencies of the two polymorphisms satisfied the Hardy-Weinberg equilibrium. The baPWV of -1030C/T polymorphism was significantly greater in subjects with CC genotype than in subjects with CT + TT genotype (1,652 +/- 22.1 cm/s vs. 1,552 +/- 43.0 cm/s, p = 0.039); however, no significant difference was found for 1908C/T polymorphism. The baPWV was found to be significantly associated with age, body height, systolic blood pressure, and smoking habit; therefore, we next performed multiple regression analysis including these parameters, and found an independent, significant association between baPWV and -1030C/T polymorphism. Conclusion: Promoter -1030C/T polymorphism of LMNA is a possible genetic predisposition to arterial stiffness in the Japanese population.