<i>NR1D1 (REVERBalpha)</i> may be novel candidate gene for coronary artery disease in men: Differential effects of <i>NR1D1</i> polymorphisms by gender

Circadian rhythms are strongly linked to cardiometabolic syndromes such as coronary artery disease (CAD). <i>NR1D1(REVERBalpha)</i> regulates lipid metabolism and circadian clock. This study investigated possible associations between the <i>NR1D1</i> rs2314339 C > T and rs72836608 C > A polymorphisms and metabolic parameters in 126 CAD patients and 125 controls. Allelic discrimination was performed by Real-Time PCR using TaqMan Genotyping Assays. The rs2314339-CC and rs72836608-AA genotypes were associated with an increased risk of CAD (<i>p</i> < 0.05), which varied according to cardiovascular risk factors. The rs72836608-A allele and rs2314339-CC genotypes were associated with an increased risk of CAD in healthy-weight, non-diabetic, normolipidemic, and male patients (<i>p</i> < 0.05). Additionally, the rs72836608-A allele was associated with an elevated risk of CAD in patients with hypertension (<i>p</i> = 0.016). Subgroup analysis by gender showed that the rs72836608-A allele (<i>p</i> = 0.018), the rs2314339-CC genotype (<i>p</i> = 0.008), hyperlipidemia (<i>p</i> = 0.001), hypertension (<i>p</i> = 0.001), and type 2 diabetes mellitus (T2DM) (<i>p</i> = 0.001) were associated with an increased risk of CAD in men. Nevertheless, the presence of hypertension (<i>p</i> = 0.008), hyperlipidemia (<i>p</i> = 0.025), and T2DM (<i>p</i> = 0.001) were significantly associated with CAD risk in the females. Multivariate regression analysis revealed that the rs72836608-A allele (<i>p</i> = 0.034), male gender (<i>p</i> = 0.01), hyperlipidemia (<i>p</i> = 0.008), hypertension (<i>p</i> = 0.001), and T2DM (<i>p</i> = 0.001) were associated with an increased risk for CAD in the overall cohort. The findings suggest that both polymorphisms may be associated with an increased risk of CAD, particularly in men, and may be influenced by factors including age and other cardiovascular risk factors.