Cytochrome P4501A1 polymorphisms in the Amerindian and Mestizo populations of Mexico

Several polymorphisms in the CYP1A1 locus have been identified and their genotypes appear to exhibit population frequencies that depend on ethnicity. We studied two CYP1A1 polymorphic sites (position 4889 and 6235) in a group of 212 unrelated healthy individuals belonging to three different Mexican populations (106 Mexican Mestizos, 52 Teenek and 54 Mayos). Comparison among Mexican populations showed increased frequency of the *Ile allele (A on position 4889) in Mexican Mestizos when compared to Amerindians (p < 0.05). The analysis of position 6235 showed increased frequencies of *m2 (C in this position) allele in Teenek when compared to Mestizos and Mayos (p < 0.05) and of *m2/*m2 genotype when compared to Mestizos (p < 0.05). Amerindian populations (from Mexico and South America) presented the lowest frequencies of *Ile (position 4889) and *m1 (position 6235) alleles, however these frequencies vary according to the ethnic group studied. Mexican Amerindian groups together with other South Amerindian populations showed the highest frequencies for *Val at position 4889 and the *m2 allele at position 6235. The present study corroborates the high frequencies of*Val and *m2 alleles in the Amerindian populations and detects some differences between Mexican populations that correlate with linguistic differences. Our data could be helpful in understanding the distribution of these polymorphisms and in clarifying their roles as genetic and evolution markers in Amerindian populations.     

Allele frequency distribution of CYP2C9*2 and CYP2C9*3 polymorphisms in six Mexican populations

Allele frequency differences of functional CYP2C9 polymorphisms are responsible for some of the variation in drug response observed in human populations. The most relevant CYP2C9 functional variants are CYP2C9*2 (rs1799853) and CYP2C9*3 (rs1057910). These polymorphisms show variation in allele frequencies among different population groups. The present study aimed to analyze these polymorphisms in 947 Mexican-Mestizo from Mexico City and 483 individuals from five indigenous Mexican populations: Nahua, Teenek, Tarahumara, Purepecha and Huichol. The CYP2C9*2 allele frequencies in the Mestizo, Nahua and Teenek populations were 0.051, 0.007 and 0.005, respectively. As for CYP2C9*3, the allelic frequencies in the Mestizo, Nahua and Teenek populations were 0.04, 0.005 and 0.005, respectively. The CYP2C9*2 and CYP2C9*3 alleles were not observed in the Tarahumara, Purepecha and Huichol populations. These findings are in agreement with previous studies reporting very low allele frequencies for these polymorphisms in American Indigenous populations.     

Beta1 adrenergic receptor polymorphisms Arg389Gly and Ser49Gly in the Amerindian and Mestizo populations of Mexico

The beta1 adrenergic receptor genotypes (Ser49Gly and Arg389Gly) were determined in 190 individuals from 3 Mexican populations. Mestizos and Teenek present the highest frequencies for the *Arg allele and the lowest frequencies for the *Gly allele (Arg389Gly) compared to European, Asian, and African populations. Mayos present the highest frequency for the *Gly allele. The knowledge of the distribution of these alleles could help define the significance of these polymorphisms as genetic susceptibility markers in Amerindian populations.     

Distribution of AB0 and RH blood group alleles in different populations of southern Punjab, Pakistan.

The analysis of a sample of 1632 individuals from patients of the Nishtar Teaching Hospital, Multan, suggests that different ethnic groups (Araeen, Mughals, Syed, Jat, Rajputs, Baloch and Pathan) are not significantly different from another with regard to the distribution of RH blood group alleles (RH*d around 0.30). The distributions of the AB0 blood group alleles suggest that different ethnic groups are not significantly different from the average alele frequencies (AB0*A = 0.23, AB0*B = 0.33, AB0*0 = 0.47) except for the Pathan ethnic group (AB0*A = 0.35, AB0*B = 0.47, AB0*0 = 0.27). The populations of different geographic areas are not significantly different from the average allele frequencies, except for the southern district of Rahim Yar Khan (AB0*A = 0.12) and the northern district of Sahiwal (AB0*A = 0.19). The populations of Sahiwal (RH*d = 0.35) and Muzaffargarh (RH*d = 0.36) yield significantly different allele frequencies at the RH locus. The interpopulation differences can be explained by the geographic distance. There is a significant difference in the frequencies of the AB0 alleles between rural and urban populations, suggesting that rural populations maintain their isolation from urban populations. Rural and urban populations are not significantly different from one another concerning the allele frequencies at the RH locus.     

Cytochrome P4502C9 (CYP2C9) allele frequencies in Canadian Native Indian and Inuit populations.

CYP2C9 is the major P450 2C enzyme in human liver and contributes to the metabolism of a number of clinically important substrate drugs. This polymorphically expressed enzyme has been studied in Caucasian, Asian, and to some extent in African American populations, but little is known about the genetic variation in Native American populations. We therefore determined the 2C9*2 (Arg144Cys) and 2C9*3 (Ile359Leu) allele frequencies in 153 Native Canadian Indian (CNI) and 151 Inuit subjects by PCR-RFLP techniques. We also present genotyping data for two reference populations, 325 Caucasian (white North American) and 102 Chinese subjects. Genotyping analysis did not reveal any 2C9*4 alleles in the CNI, Inuit, Caucasian, or Chinese individuals. The 2C9*2 allele appears to be absent in Chinese and Inuit populations, but was present in CNI and Caucasian subjects at frequencies of 0.03 and 0.08-0.15, respectively. The 2C9*3 allele was not detected in the Inuit group, but occured in the CNI group (f = 0.06) at a frequency comparable to that of other ethnic groups. This group of Inuit individuals are the first population in which no 2C9*2 or *3 alleles have been detected so far. Therefore, these alleles may be extremely rare or absent, and unless other novel polymorphisms exist in this Inuit group one would not anticipate any CYP2C9 poor metabolizer subjects among this population.     

Salivary protein polymorphism in Kenya: evidence for a new AMY1 allele

Salivary protein polymorphism was studied in 200 schoolboys, mainly Kisii and Luo from Kenya, East Africa. The frequencies of PR, PA, DB, PB and AMY1 genes were as follows: PR*1: 0.66, PA*(+): 0.18, DB*(+): 0.55, PB*2: 0.12, AMY1*A2: 0.008, AMY1*E: 0.03. These frequencies were compared with other population data, in particular from West African and US Negroes. The most interesting finding with respect to the gene frequencies is the low PB*2 frequency and the absence of AMY1*3 in Kenya. Furthermore, a new phenotype in the AMY1 system was described which suggests the presence of an allele with an estimated frequency of 0.02.     

Study of five haemogenetic markers (Gc, C3, Bf, Ag, and GALT) in six Indonesian populations and in 12 subgroups of Balinese

In various ethnic groups of the Indonesian archipelago and of Bali, the polymorphisms of the serum proteins Gc globulin (vitamin D-binding protein), C3 (complement component 3), Bf (complement factor B), Ag x,y (lipoprotein allotypes), and of the red cell enzyme system GALT (galactose-1P-uridyltransferase) were analysed. Among the studied proteins, the Gc system was the most informative one for the anthropologist. Besides considerable differences of frequencies of the common alleles Gc*1F, Gc*1S and Gc*2, a number of rare alleles (1A1, 1A3, 1A8, 1A9, 1A12, 1C2, 1C21, 1C24, and 2C8) and some new ones (1C28, 1C29, 1C30, 2C9) were observed. The presence of Gc*1A1 demonstrates the relationship to the Australo-Melanesian populations, but Mongolian variants (1A3, 1A8, 1A9, 1C2) were also encountered. Within the C3 system a very high frequency of the C3*S allele was observed in all populations. The rare alleles C3*F0.55, C3S1, and C3*S0.5 were observed in some groups. A new allele (C3*F0.35) was detected in a Chinese individual and in a nobleman from Bali. The frequency of the Bf*F allele was rather low in general, and the Bf*S0.7 allele was found in three Indonesian individuals only. The Ag*(x) frequencies were rather high, as it is known for Asiatic populations. Variability among subgroups was not very pronounced. The GALT*2 allele (Duarte variant of the enzyme) was observed very rarely; however, it was present in several populations. Enzyme activities could not be determined, and therefore we cannot tell whether the galactosaemia gene (GALT*0) was present or not.     

Genetic polymorphism of group-specific component/vitamin-D-binding protein subtypes in six populations from north-eastern China

On six populations from North-Eastern China the frequencies of Gc subtypes were studied by isoelectric focusing on ultra-thin polyacrylamidegel followed by the improved sulfosalicylic acid precipitation. The following Gc subtype allele frequencies could be observed in the Han (Harbin), Ewenki, Tahur, Mongolian, Oroquen and Xibe populations: Gc*1F = 0.4246, 0.4941, 0.4479, 0.4077, 0.4606 and 0.4503; Gc*1S = 0.2587, 0.2936, 0.3151, 0.2822, 0.3370 and 0.3035; Gc*2 = 0.3065, 0.2064, 0.2266, 0.3006, 0.2022 and 0.2388. In addition to this 16 individuals of five populations showed rare Gc variant alleles (1A3, 1A8, 1A9, 1A14, 1C?).     

Transferrin C subtypes and ethnic heterogeneity in Sweden

Transferrin (TF) C subtypes were studied in Swedish Lapps (Saami) and in Swedes from northern, central and southern Sweden, and the allele frequencies were compared with those in other European populations. The Swedish Lapps were found to have the lowest frequency of the TF*C3 allele (1-2%) so far observed in Europe. Most European populations have TF*C3 allele frequencies between 5 and 7%. Finns differ by having high TF*C3 frequencies (13-14%). The relatively high TF*C3 frequencies found in northeastern Sweden (13%) and in central Sweden (9%) are most likely due to eastern influence. Unlike other genetic markers of eastern influence (e.g. TF*DCHI), which are of Asiatic Mongoloid origin, TF*C3 appears to originate from Finno-Ugric populations.     

Allele frequency distributions of -174G/C polymorphism in regulatory region of interleukin 6 gene (IL6) in Russian and worldwide populations

Allele and genotype frequencies of the ?174G/C polymorphism (rs1800795) in the regulatory region of the IL6 gene, which encode anti-inflammatory cytokine interleukin 6, were determined in seven populations representing five ethnic groups from the European part of Russia (440 individuals), as well as in small cohorts that represent populations from 24 countries of Africa and Eurasia (365 individuals). The maps of the geographic distribution of the ?174G/C allele frequencies were constructed based on personal (22 populations) and the literature data (66 populations), and the data from dbSNP database obtained by the HapMap project (10 populations). The frequency of the ?174G allele varied from 45 to 100% and was characterized by nonrandom geographic distribution. These data could reflect the adaptive load of the alleles examined, which was different in different regions of the world. It is suggested that the level of pathogen prevalence is one of the environmental factors that determine different adaptive values of the IL6*-174G/C alleles. This suggestion is supported by a positive correlation between the ?174G allele frequency and level of pathogen prevalence calculated based on historical data (R = 0.768; p < 0.0001).     

Distribution of transferrin subtypes in Tarragona (east Spain).

The distribution of transferrin (TF) subtypes was determined by isoelectric focusing of sera from 284 unrelated individuals from Tarragona (south of Catalonia). The allele frequencies observed, TF*C1 = 0.805, TF*C2 = 0.162, TF*C3 = 0.026 and TF*B = 0.007 were similar to those reported for other Spanish populations.     

Transferrin subtypes in 11 south China minority populations.

Transferrin subtypes were determined by isoelectric focussing (IEF) in a total of 2,121 individuals from 11 South China minority populations. The C1, C2 and DCHI alleles were present in all the populations; B alleles were lacking, C4 was found in 3 populations and C3 in 6. C2 and C4 allele frequencies are notable in these minority groups. The frequency of the C2 allele was higher (0.25-0.38) than that of Han Chinese (0.18-0.25). In Bai the C2 frequency was as high as 0.38. The C4 allele was present at a low frequency (less than 0.01), which suggests that this allele probably existed in the ancestral Mongoloid population at a low frequency and increased in frequency in Amerindians due to genetic drift or other factors.     

Acid phosphatase, adenosine deaminase and esterase D polymorphisms in the Spanish Basque population.

The 3 red-cell polymorphic systems acid phosphatase (ACP), adenosine deaminase (ADA) and esterase D (ESD) have been studied in a random sample of 1,112 individuals from the Basque country: The allelic frequencies obtained were ACP*A = 0.275, ACP*B = 0.718 and ACP*C = 0.007; ADA*2 = 0.021, and, ESD*2 = 0.066. The allelic frequencies have been compared with those of other Basque and other European populations. In comparison with Basques, significant differences were detected only for ACP, whereas as regards other Europeans significant differences were obtained with practically all the populations compared for the 3 genetic systems studied. The low values of the less frequent alleles, especially that for the ACP*C allele which is the lowest reported in Europe, are noteworthy.     

Molecular genetic diversity in 5 populations of Madhya Pradesh, India

This paper presents data on the distribution of 3 amplified fragment length polymorphisms (D1S80, APOB, and YNZ22) in 5 populations of Central India. Using the polymerase chain reaction technique, 3 caste (Brahmin, Khatri, and Dhimer) and 2 tribal (Gond and Baiga) populations were studied for the 3 loci. The allelic variations observed in the caste populations are compatible with those of many Caucasian populations, but the caste populations showed significant overall and interpopulation variability within the region. D1S80 allele *24 varied from 32% (Dhimers) to 42% (Brahmins). Allele *18 was not observed in Baiga tribal populations, but in caste populations it varied from 11% (Dhimers) to 24% (Brahmins). Both tribal populations showed higher frequencies of allele *31 (17%-18%). For APOB, caste populations again showed bimodal distribution of alleles *35 and *37, but in tribal populations higher allele numbers (*47, *49) were also frequent. For YNZ22, extensive variation was observed for all populations studied. Allele *4 was the most common in caste populations, while alleles *2, *7, and *10 were prominent in tribal populations. The level of gene differentiation is not very high for the 3 systems studied in the 5 populations. Overall, allele frequency distribution, heterozygosity, and genetic diversity analysis show that the genetic diversity observed is socially and geographically structured.     

The prevalence of VKORC1 1639 G>A and CYP2C9*2*3 genotypes in patients that requiring anticoagulant therapy in Turkish population

The aim was to investigate the prevalence of VKORC1 and CYP2C9 genotypes in patients requiring anticoagulant therapy in two different region’s populations of Turkey. The recent cohort included 292 patients that needed anticoagulant therapy, and who had a history of deep vein thrombosis and/or pulmonary artery thromboembolism. Genomic DNA was isolated from peripheral blood samples and the StripAssay reverse hybridization or Real Time PCR technique was used for genotype analysis. Genotypes for CYP2C9 were detected as follows: 165 (56.5?%) for CYP2C9*1/*1, 67 (23.0?%) for CYP2C9*1/*2, 25 (8.6?%) for CYP2C9*1/*3, 9 (3.0?%) for CYP2C9*2/*2, 21 (7.2?%) for CYP2C9*2/*3, 5(1.7?%) for CYP2C9*3/*3 for CYP2C9 and the allele frequencies were: 0.723 for allele*1, 0.182 for allele*2 and 0.095 for allele*3 respectively. Genotypes for VKORC1 were detected as follows: 64 (21.9?%) for GG, 220 (75.4?%) for GA and 8 (2.7?%) for AA alleles. The G allele frequency was detected as 0.596, and the A allele frequency was 0.404. The VKORC1 1639 G>A and CYP2C9 mutation prevalence and allele frequency of the current results from two different populations (Sivas and Canakkale) showed similarly very variable profiles when compared to the other results from the Turkish population.     

Distribution of plasma alpha-1-B-glycoprotein phenotypes in several Mongoloid populations of East Asia

The distribution of plasma alpha 1B-glycoprotein (alpha 1B) phenotypes was determined by a simple method of two-dimensional electrophoresis followed by protein staining in a group of 1,154 individuals from 8 Mongoloid populations of East Asia. The sample comprised 581 Chinese from different localities (Singapore: 204; Taiwan: 150; Fujien and Hopeh provinces of eastern China: 146 and 81), 155 Koreans, 155 Filipinos, 152 Thais and 111 Malays. Altogether, 6 different alpha 1B phenotypes (1-1, 1-2, 2-2, 1-3, 2-3, and 1-6) were observed. The alpha 1B allele frequencies were very similar in all of the populations. The frequency of A1B*1 varied from 0.89 to 0.91 and that of A1B*2 from 0.08 to 0.10. The A1B*3 allele, reported previously only in American blacks, was observed with a frequency range of 0.003-0.01 in 3 of the Chinese populations, in Koreans and in Malays. A new alpha 1B allele (A1B*6) was observed in 2 Chinese individuals.     

Apolipoprotein E polymorphism in the Indian and Mestizo populations of Mexico

Apolipoprotein E (APOE) genotypes were determined in 75 Mazatecan Indians and 83 Mexican mestizos. APOE allele and genotype frequencies in Mazatecans and mestizos were similar, with high frequencies of the APOE*3 allele (0.900 and 0.915, respectively) and the E3/3 genotype (0.813 and 0.831, respectively) and an absence in both samples of the APOE*2 allele. Our data are similar to those previously described for Mexican-American and Mayan populations, which show the highest frequency worldwide of the APOE*3 allele and the E3/3 genotype. Mazatecans and mestizos also show a decreased frequency of the APOE*4 allele when compared to other Amerindian groups. The absence of the APOE*2 allele has also been reported in other Amerindian groups such as Mayans and Cayapa, whereas in Caucasians the average frequency of this allele is about 8%. Our data are in agreement with previous reports showing absence of the APOE*2 allele in Native American groups. These findings suggest that the APOE*2 allele was absent in humans from northern Asia who settled in the Arctic and populated the American continent.     

Apolipoprotein A1 gene polymorphisms at the -75 bp and +83/ 84 bp polymorphic sites in healthy Omanis compared with world populations

The relative frequencies of the *A allele of the APOA1 gene at -75 bp (M1-) and the C or T +83/+ 84 bp allele (M2-) varied significantly between populations. We found the frequencies of M1- and M2- to be 0.22 and 0.067, respectively, in 150 healthy Omanis. These frequencies were compared to frequencies found in other world populations.     

Polymorphism of the HFE gene associated with hereditary hemochromatosis in populations of Russia

Expression of hereditary hemochromatosis as well as predisposition to iron overload syndrome and sporadic porphyria cutanea tarda are currently believed to be associated with the inheritance of certain allelic variants of the HFE gene. Allele frequencies of the C282Y (845A) and H63D (187G) mutations in the HFE gene in human populations of different races are remarkably different, and the prevalence of the S65C (193T) mutation is still poorly studied. In the present study we estimated allele frequencies of HFE mutations in Russians and in a number of Siberian ethnic indigenous populations. In Russians, allele frequencies of the C282Y, H63D and S65C mutations were 3.7, 13.3 and 1.7%, respectively. These values were similar to those observed in populations of Europe. The C282Y mutation was not detected in the population samples of Siberian ethnic groups, including Mansis, Khantys (Finno-Ugric group), Altaians, and Nivkhs (Mongoloids), suggesting that the frequency of this allele in the populations examined was lower than 1%. The frequency of the C282Y allele in the Tuvinian and Chukchi samples (Mongoloids) constituted 0.45 and 0.8%, respectively. Furthermore, pedigree analysis of both Chukchi carriers discovered showed that some of their ancestors were from other ethnic groups. Low frequencies of this allelic variant is typical of many Eastern Asian populations, which are also characterized by rather low frequencies of the H63D variant. In contrast, in some ethnic groups of Western Siberia allelic frequency of the H63D mutation is rather high, constituting 8.7% in Altaians, 15.5% in Mansis, and 11.3% in Khantys. The frequency of this allele in Tuvinians, Nivkhs, and Chukchis constituted 5, 4.7, and 0.8%, respectively. These findings make it possible to estimate the proportion of individuals predisposed to iron overload syndrome in different Russian ethnic groups. The HFE allele frequency distribution patterns observed in the populations examined pointed to pre-Celtic appearance of the CY82 allele. It also provides elucidation of the evolutionary genetic relationships between Siberian ethnic groups and the contemporary populations of Eastern and Western Europe.     

The plasminogen polymorphism in South African Negro populations: genetics and anthropogenetics

Summary Genetic polymorphism of human plasminogen (PLG) was investigated in 1252 unrelated individuals from eight South African Bantu-speaking Negro tribes. PLG phenotypes were determined by isoelectric focusing (pH 3.5–9.5 and 5–8 gradients) of neuraminidase-treated samples and subsequent detection by caseinolytic overlay or immunoblotting with specific antibody. No significant difference in the distribution of PLG alleles among the eight ethnic groups was observed. The combined allele frequencies of the common alleles in South African Negroes were 0.6977 for PLG*A, 0.2736 for PLG*B. In addition, six rare alleles were seen: PLG*A3, *A1, *M2, *B1, *B2, *B3. The rare variant PLG*B2 was proven to segregate by autosomal Mendelian inheritance in a family. The combined frequency for the rare alleles was 0.0287. The distribution of phenotypes in the total population sample was found to be in Hardy-Weinberg equilibrium. A striking difference in PLG allele distribution between Negroes from South Africa and published Negroid frequencies from North America could be observed. This difference was also seen in comparison with Mongoloid populations; in contrast, PLG frequencies for South African Negroes were similar or almost identical to known Caucasoid distributions.