Porphyrias are due to heme enzymes deficiencies: Porphobilinogen deaminase in Acute Intermittent Porphyria (AIP) and Uroporphyrinogen decarboxylase (URO-D) in Porphyria Cutanea Tarda (PCT). In Argentina, AIP and PCT are the most common hepatic Porphyrias. Many triggering factors are involved such as therapeutic medications, alcohol, abuse drugs, estrogens and iron levels. Nuclear receptors such as the Pregnane X Receptor (PXR) are key regulators of ABC drug transporters and CYP3A4. Previously we investigated the role of ABCB1 and ABCG2 in AIP and PCT triggering. The aim was to continue analyzing variants of NR1I2 gene that encodes for PXR. For this purpose rs12721613 (NM_022002.3:c.196C>T) and rs2472677 (NM_003889.4:c.-22–7659C>T) variants were genotyped in Control, symptomatic AIP (S-AIP), asymptomatic AIP (L-AIP) and acquired PCT (A-PCT) by PCR-RFLP. Individuals signed informed consent. When AIP was evaluated, c.196C>T allelic frequency for S-AIP (0.129) was lesser than Control (0.288, p<0.01) and L-AIP (0.273, p<0.05). A different genotypic profile was observed: S-AIP showed a less value in heterozygosis (25.93%) vs Control (45.45%, p<0.01) and L-AIP (48.48%, p<0.01); TT had in S-AIP a null value and very low in both Control (6%) and L-AIP (3%). For c.-22–7659C>T, no differences were found in the allelic and genotypic frequencies among AIP groups and Control. In PCT cohort, T allele frequency for c.196C>T was very low (0.021, p<0.01) respect to Control (0.288). Genotypic frequency in heterozygosity was lower in PCT group (4.14%, p<0.01) than in Control (31.57); concordantly a high proportion was observed in homozygosity for wild type in this Porphyria. For c.-22–7659C>T, allelic frequencies were similar for PCT and Control while genotypic profile showed less proportion of CT (36.4%, p<0.05) in PCT and high levels although no significant for TT vs Control. In conclusion, for AIP, the higher presence in latent patients of c.196C>T would suggest that T could be a protector allele, probable related to a minor demand of heme due to the downregulation of PXR on CYP3A4. For A-PCT, the major presence of TT genotype found in c.-22–7659C>T could be related to its onset considering that the negative regulation of PXR on ABCB1 and CYP3A4 transcription affects detoxification and transport of xenobiotics promoting a hepatotoxic environment that inhibits URO-D activity. Considering the importance to study local population, further investigation to compare allele frequencies in Argentinean Control cohort using gnomAD was done. The frequency of rs2473677 was significantly higher in Argentinean population than in Americans who have null value, and Africans, being similar to Europeans and global population. For rs12721613, T frequency was higher in Argentina than in the other populations included global one. Finally, NR1I2 gene variants could be considered as a possible modulator in the pharmacological induction of Hepatic Porphyrias.