MDR1 Haplotype Frequencies in Japanese and Caucasian, and in Japanese Patients with Colorectal Cancer and Esophageal Cancer

Abstract

   The genotype frequencies of MDR1 T-129C, C1236T, G2677A,T and C3435T SNPs were compared in 154 healthy Japanese and 100 healthy Caucasians to provide basic information on the inter-ethnic differences of pharmacotherapeutic outcome. The variants were found at allelic frequencies of 5.5%, 65.6%, 16.6%, 40.6% and 40.6%, for T-129C, C1236T, G2677A, G2677T and C3435T, respectively, in Japanese, and at 5.1%, 45.9%, 3.6%, 46.4% and 56.6%, respectively, in Caucasians, with a statistically significant difference for C1236T, G2677A,T and C3435T (p<0.001). G2677A was about 5-fold more frequent in Japanese than Caucasians. These genotype frequencies were also investigated in 95 Japanese patients with colorectal cancer (CRC) and esophageal squamous cell carcinoma (ESCC), but no significant difference was detected, when compared with healthy Japanese subjects. The haplotype frequency reached a total of about 85% in Japanese with the following 4 major haplotypes;
  T^-129-T¹²³⁶-T²⁶⁷⁷-T³⁴³⁵ (36.1%), T^-129-T¹²³⁶-G²⁶⁷⁷-C³⁴³⁵ (22.5%),
  T^-129-C¹²³⁶-G²⁶⁷⁷-C³⁴³⁵ (14.2%) and T^-129-C¹²³⁶-A²⁶⁷⁷-C³⁴³⁵ (13.3%). The second and fourth haplotypes were hardly inferred in Caucasian, whereas T^-129-C¹²³⁶-G²⁶⁷⁷-T³⁴³⁵ (12.8%) was found to be Caucasian-specific. There was a tendency for higher frequencies of the T^-129/C-¹²⁹-C¹²³⁶-A²⁶⁷⁷-C³⁴³⁵ haplotype in Japanese CRC patients and T^-129-T¹²³⁶-T²⁶⁷⁷-T³⁴³⁵ haplotype in Japanese ESCC patients, compared with that in healthy Japanese subjects.