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)

Abstract

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.

Association of self-reported race/ethnicity and genetic ancestry with arterial elasticity: the Multi-Ethnic Study of Atherosclerosis (MESA)

“…The significant association of genetic ancestry with arterial elasticity in this study is supported by several studies and reviews of genetic variants associated with measures of vascular dysfunction(32–50), including variants in the angiotensinogen, beta-adrenergic receptor, and advanced glycation endproducts receptor genes, as well as several genes involved in cardiac function and structure; however, these studies were in participants of European descent. Our study suggests that there is genetic heterogeneity among both Hispanics and African-Americans, and that this heterogeneity is important in determining measures of vascular dysfunction.…”

Association Between DNA Methylation and Blood Pressure: A 5-Year Longitudinal Twin Study

“…A mutant of the LMNA gene has been reported to be associated with a blunted vasodilator response and elevated SBP/DBP levels. 56,57 cg11376147 is in the enhancer region of SLC43A1 , and although the impact of enhancer DNA methylation on gene expression is complex, previous literature has indicated that methylation of enhancer elements influences tissue-specific gene expression. 58 SLC43A1 is related to metabolic phenotypes, particularly lipids and adiposity, which may synergistically affect the pathogenesis of hypertension.…”

Genome-wide pharmacogenomic study of citalopram-induced side effects in STAR*D

“…64, 65 This relatively frequently studied gene has been linked to several cancers including non-small-cell lung and colorectal, 66, 67 as well as cardiovascular pathophysiology. 68 LAMA1 has also been associated with pharmacogenetic moderation of thiazolidinedione-induced side effects to diabetes treatment and, 69 more relevantly, with moderating the effects of antidepressant buproprion on smoking cessation. 70 Thus, robust GWAS support and prior evidence of antidepressant moderation suggest LAMA1 as a plausible candidate for future pharmacogenetic and functional analyses.…”