ABCMdb

PMID: 19546880

Yen-Revollo JL, Van Booven DJ, Peters EJ, Hoskins JM, Engen RM, Kannall HD, Ofori-Adjei D, McLeod HL, Marsh S
Influence of ethnicity on pharmacogenetic variation in the Ghanaian population.
Pharmacogenomics J. 2009 Dec;9(6):373-9. Epub 2009 Jun 23., [PubMed]

Sentences

No. Mutations Sentence Comment

27 ABCG2 p.Gln141Lys Many existing US studies were performed using primarily Caucasian subjects (ABCG2 Q141K, CYP3A5*3C, DPYD*2A GSTP1 I105V, NAT2*6, TPMT 719A4G, TYMS 1494del).17-20 Some studies included allele frequencies from different ethnicities such as European-Americans, African-Americans, Asian- Americans, and Hispanic-Americans (ABCB1 3435C4T, CYP2C19*2, CYP2C9*2 and *3, CYP3A4*1B, and UGT1A1 - 3156G4A).18,21 Results All of the genotypes were found to be in Hardy-Weinberg equilibrium. Login to comment 42 ABCG2 p.Gln141Lys ABCG2 p.Gln141Lys Table2GenotypesandallelefrequenciesofpharmacogeneticallyrelevantpolymorphismsobservedintheGhanaianpopulation(%inparenthesis) ABCB1 3435C4T ABCG2 Q141K CYP2C19 *2 CYP2C9 *2 CYP2C9 *3 CYP3A4 *1B CYP3A5 *3C DPYD *2A GSTP1 I105V NAT2 *14 NAT2 *6 TNFa À238G4A TPMT 719A4G TYMS 1494del UGT1A1 À3156G4A Total# genotyped 861919828845835787864893837800850850863799853 #majorallele homozygous 671(78)905(98.5)578(70)843(99.8)834(99.9)34(4)644(75)893(100)224(27)643(80)467(55)820(96.5)751(87)287(36)382(45) #heterozygous176(20)13(1.4)224(27)2(0.2)1(0.1)271(34)201(23)0(0)392(47)150(19)314(37)27(3.2)106(12)325(41)360(42) #minorallele homozygous 14(2)1(0.1)26(3)0(0)0(0)482(61)19(2)0(0)221(26)7(1)69(8)3(0.3)6(1)187(23)111(13) Majorallele frequency 0.880.990.831.001.000.220.861.000.500.900.730.980.930.560.66 Minorallele frequency 0.120.010.170.000.000.780.140.000.500.100.270.020.070.440.34 Table3ComparisonofliteraturereportedallelefrequenciesofpharmacogeneticallyrelevantpolymorphismsinAfricannationscomparedwiththeGhanaian population MinoralleleABCB1 3435C4T ABCG2 Q141K CYP2C19 *2 CYP2C9 *2 CYP2C9 *3 CYP3A4 *1B CYP3A5 *3C DPYD *2A GSTP1 I105V NAT2 *14 NAT2 *6 TNFa -238G4A TPMT 719A4G TYMS 1494del UGT1A1 -3156G4A TAATCGGAGAAAGinsTTAAAGA Ghana(total)0.120.010.170.000.000.780.140.000.500.100.270.020.070.440.34 Yoruba (HapMap)28 0.110.167000.7460.1500.3750.0920.175N/A0.05 WestAfrica Ghana0.1718 0.8118 018 Benin0.1318 0a18 BurkinaFaso0.0222 Cameroon0.4618 Gabon0.10*23 Guinea-Bissau0.8118 Nigeria0.8718 0.0618 Senegal0.7818 0.3118 0.124 0.1724 TheGambia0.21*18 0.5318 0.06*30 EastAfrica Egypt0.4*18 0.06*18 0.18*a18 018 0.27*18 0.02*18 Ethiopia0.07*18 0.06*a18 Kenya0.1718 0.1518 0.0518 Sudan0.27*18 0.03*25 0.2925 0.08*31 Tanzania0.1818 0.16*18 0.1226 0.2126 SouthAfrica Namibia0.0718 SouthAfrica0.118 0.8418 0.1918 0.14*18 0.0432 Zimbabwe0.1318 0.78*18 0.24*18 0.1426 0.2126 NorthAfrica Algeria0.84*18 Tunisia018 0.34*18 0.2927 CentralAfrica CentralAfrican Republic 0.1118 Democratic Republicof theCongo 0.0718 UnitedStates0.54*18 0.14*17 0.1318 0.2*a18 0.04*18 0.91*18 018 0.28*18 0.2719 0.06*33 0.0418 0.32*20 0.3021 a CYP2C9*2/*3combinedfrequency. Login to comment 53 ABCG2 p.Gln141Lys The results from this study strongly suggest that Ghanaian, Table 4 Self-reported ethnicity of 934 Ghanaian samples Tribe N Median Age (Min-Max) Male:Female Akwapim 90 25 (16-51) 51:39 Ashanti 103 23 (17-50) 54:49 Ewe 183 24 (17-51) 97:86 Fanti 160 24 (17-58) 85:75 Ga 183 25 (17-54) 113:70 Other 215 24 (17-57) 135:80 Total 934 24 (16-58) 535:399 Table5AllelefrequenciesofpharmacogeneticallyrelevantpolymorphismsinfiveGhanaiantribes MinoralleleABCB1 3435C4T ABCG2 Q141K CYP2C19 *2 CYP2C9 *2 CYP2C9 *3 CYP3A4 *1B CYP3A5 *3C DPYD *2A GSTP1 I105V NAT2 *14 NAT2 *6 TNFa -238G4A TPMT 719A4G TYMS 1494del UGT1A1 -3156G4A TAATCGGAGAAAGinsTTAAAGA Ghana(total)0.120.010.170.000.000.780.140.000.500.100.270.020.070.440.34 Akwapim0.150.010.160.000.000.730.140.000.490.080.210.020.060.400.33 Ashanti0.090.000.150.000.000.790.110.000.490.100.280.000.070.410.30 Ewe0.130.010.180.000.000.850.130.000.530.110.250.020.070.420.35 Fanti0.130.000.140.000.000.810.120.000.490.100.280.020.080.440.34 Ga0.090.000.180.000.000.750.150.000.490.120.270.030.060.480.35 and other West African populations, may have very different responses, particularly with regard to efficacy and toxicity, to drug treatment regimens that were optimized in US cohorts. Login to comment