Nesfatin-1 (NUCB2) gene, was introduced as a novel satiety factor involves in the control of energy homeostasis in the hypothalamus. Since NUCB2/nesfatin-1 has an effect on diabetes and obesity, it is a candidate gene that can be responsible for causing coronary artery disease (CAD).Therefore, we aimed to identify the association between rs214101 (C/T) SNP of NUCB2 gene and the possible amplified effects of this genetic variation together on the development risk of CAD in this study.This study was carried out in 110 patients with CAD, and 69 CAD-free controls. The NUCB2/nesfatin-1 rs214101 genotypes were analysed by PCR-RFLP technique. The CC genotype frequency of the NUCB2 rs214101 was greater in control group than CAD group (34.8% vs.52.7%; P = 0,019).The CC-genotype was associated with low serum HDL-C level compared to T allele in female CAD subgroup (P = 0.031), but, not in males. Unlike the CAD group, it was observed that the male control subjects carrying CC genotype have higher serum HDL-cholesterol and diastolic blood pressure levels than those with T allele (P = 0.043 and P = 0.031, respectively) but, not in females. Logistic regression analysis confirmed that the NUCB2/Nesfatin-1 rs214101 CC-genotype is associated with low serum HDL-cholesterol in femaleCADpatients. Our results suggest that the CC genotype of NUCB2 rs214101 may contribute to susceptibility CAD risk in relation to low HDL-C and that the genetic effect could differ by gender.