Global analysis of genetic variation in SLCO1B1

Introduction: Organic anion transporting polypeptide 1B1 (OATP1B1), encoded by the SLCO1B1 gene, mediates the hepatic uptake of endogenous compounds and xenobiotics, including drugs. The aim of this study was to investigate the diversity of the SLCO1B1 gene at the global level. Materials and methods: Distribution of SLCO1B1 alleles was determined in 941 individuals from 52 populations comprising Africa, the Middle East, Asia, Europe, Oceania and the Americas. DNA samples were genotyped at 12 variant sites spanning the entire gene by TaqMan 5´nuclease allelic discrimination assays. Results: The frequency of the low-activity c.521T>C variant varied markedly between populations. The lowest frequencies were observed in Oceania (0.0%; 95% CI: 0.0–6.4%) and sub-Saharan Africa (1.9%; 95% CI: 0.7–4.8%), and the highest frequencies observed in American native populations (24%; 95% CI: 18–32%) and Europe (18%; 95% CI: 14–23%). Moreover, the c.521C allele (r = 0.505, p < 0.001) and the *1B (c.388G–c.521T; r = -0.405, p = 0.006) and *15 (c.388G–c.521C; r = 0.510, p < 0.001) haplotype frequencies correlated significantly with latitude in the northern hemisphere. Overall, SLCO1B1 genetic distances correlated significantly with geographic distances between populations, assuming likely routes of human migration out of Africa via five waypoints (r = 0.235, p = 0.001). SLCO1B1 diversity was generally far greater within than between populations. Conclusion: Functionally significant variants of SLCO1B1 are widely distributed and occur at high frequencies around the world. SLCO1B1 diversity is greater within than between populations, and genetic variation in SLCO1B1 is generally similar to that observed for other autosomal markers. However, selective pressure may have acted on SLCO1B1 during human dispersal favoring low-activity variants in the north.