Introduction: Disturbances in blood lipids levels are considered an important risk factor for cardiovascular diseases. Low serum level of HDL-C is one of these disturbances. Therefore, identifying the genes effective on HDL levels is very important. The present study investigated the relationship between LCAT gene sequence alterations and serum levels of HDL-C. Materials and Methods: Using the data of phase 4 of the TLGS study, individuals with low serum HDL-C and individuals with high serum HDL-C were identified and individual aged ≥15 from both groups, who had at least one first degree relative with the desired phenotype were finally enrolled in the study. For each Individual confounding factors, including BMI, age, sex, blood sugar and blood pressure, were determined. LCAT gene variants were determined through direct sequencing, and their relationship with HDL-C level was investigated in the Tehran lipid and glucose study (TLGS). Results: In total, 15 variants were identified. Two variants of rs5923 and Q177E, with allelic frequencies of 5.87% and 4.7%, respectively, were identified in both groups, although, they were significantly higher in the low HDL subjects. Eleven variants were reported for the first time, while 4 variants had already been reported in the SNP database. Conclusions: Exon regions of the LCAT gene in Tehran's population have various gene variants. Although the prevalence of a number of single nucleotide variants of this gene was higher in individuals with low serum HDL-C, after adjustment for confounding factors, the difference was not statistically significant.