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Our study investigated the role of MTHFR C677T and A1298C variants in infants with neural tube defects (NTDs) from western Mexico. Using TaqMan allelic discrimination assay, we genotyped 101 live-born patients with NTDs (cases) and 247 controls. Our findings do not support that homozygosity or heterozygosity for the variants C677T and A1298C in the MTHFR gene are associated with NTDs in infants. However, since we have the highest worldwide frequency of homozygotes for the MTHFR C677T variant, we cannot rule out that our propensity for NTDs may be related to how such gene variant interacts with other factors, mainly with our secular patterns of inappropriate folate intake.

Background: In Mexico, type 2 diabetes prevalence is 13.7%, which has a huge impact on Mexican public health. There is an urgent need to focus on the prevention of pre-diabetes to decrease the likelihood of type 2 diabetes onset. Gene variants predisposed to increase Fasting Blood Glucose (FBG) and glycosylated hemoglobin (HbA1c) levels could be helpful for prevention purposes. This study aimed to analyze the association of the G6PC2 rs560887 variant with pre-diabetes in a Mexican-Mestizo population. Methods: A cross-sectional case-control study was performed in 960 Mexican Mestizos participants. The association of G6PC2 rs560887 with pre-diabetes was analyzed by logistic regression and with Fasting Blood Glucose (FBG) and glycosylated hemoglobin (HbA1c) by linear regression. Results: The G6PC2 rs560887 variant was significantly associated with FBG (β -1.80, p=0.03), but not with HbA1c or the presence of pre-diabetes. Conclusion: The G6PC2 rs560887 loci could be a potential early marker of type 2 diabetes.

UGT1A6 catalyzes the glucuronidation of several xenobiotics and drugs widely used. Changes in the glucuronidation rate are attributed to inter-personal and inter-ethnic variations, that can impact the expression or enzyme function. Frequencies of genetic polymorphisms of UGT1A6 have been reported in another countries; however, there are no date of frequencies in the Mexican population. The aim of this work was to determine the genotypic and allelic frequencies of UGT1A6 19T˃G in a Mexican mestizo population of the state of Puebla and compare them with the frequencies observed in other populations. Peripheral blood DNA was obtained from 60 healthy adults and 19 T˃G alleles were identified by the PCR-RFLP technique. Our results were compared with those observed in other ethnic groups, and we observed that our frequencies were lower than those reported in Chinese, Korean, Japanese, Hindu, and Greek populations. These results must be considered to make decisions when choosing the drugs administered to different ethnic groups.

Leprosy, a human chronic granulomatous disease caused by Mycobacterium leprae (M. leprae), remains endemic in certain countries despite the use of multidrug therapy. Recently, several host genes modulating the immune responses to M. leprae infection have been suggested to influence the acquisition and clinical course of leprosy. Lymphoid protein tyrosine phosphatase, encoded by the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene, serves a negative regulatory role in T cell activation. The non-synonymous single-nucleotide polymorphism (SNP) rs2476601 (1858C>T) has been associated with autoimmune diseases. Here, the present study investigated if rs2476601 polymorphism was associated with leprosy in a Mexican mestizo population. Genotyping was performed in patients with leprosy (n=189) and control subjects (n=231) from regions with higher incidence of leprosy. Genotypic (P=0.44) and allelic frequencies (P=0.45) of the rs2476601 polymorphism were similar between patients and controls; genotypic frequencies were 91 vs. 94% for CC and 9 vs. 6% for CT, and the TT genotype was absent in both groups. Allelic frequencies were 96 vs. 97% for C, and 4 vs. 3% for T. In the same way, the genotypic (P=0.46) and allelic frequencies (P=0.47) from MB patients and controls were similar. In conclusion, there was a lack of association of the PTPN22 rs2476601 polymorphism with the development of leprosy, which suggests that this SNP was not a genetic risk factor for leprosy in the Mexican mestizo population studied.

Background: type-2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia, insulin resistance (IR), and abnormal fatty acid metabolism in which the CD36 receptor has been implicated in glucose and lipid dysregulation. Objective: to evaluate the contribution of polymorphism CD36 rs3211938 to metabolic profile in T2DM Mexican mestizos from western Mexico. Methods: we included 115 individuals classified as non-T2DM (NT2DM) adults and T2DM patients. Polymorphism CD36 rs3211938 was assessed by PCR-RFLP. Anthropometric and metabolic markers were measured by routine methods, and insulin and oxidized LDL (ox-LDL) were measured by ELISA. Results: the distribution of genotypes between NT2DM and T2DM patients was different (p0.001), as was the allele frequency (p = 0.002). NT2DM TG carriers showed the lowest levels of basal insulin and HOMA-IR index in comparison with TT carriers (p0.05 and p0.05, respectively). In the T2DM group TG carriers showed high BMI, WHR, and weight values (p = 0.001; p ≤ 0.05 and p0.05, respectively), and the highest levels of basal glucose, HDL-cholesterol, ox-LDL, and HOMA-IR (p0.001; p0.001; p0.001, and p = 0.001, respectively) in comparison with diabetic TT carriers. Conclusion: the CD36 rs3211938 TG genotype is associated with high levels of glucose, ox-LDL, HDL-cholesterol, and IR, and with increased BMI in Mexican mestizo T2DM patients from western Mexico.Antecedentes: la diabetes mellitus de tipo 2 (DMT2) es un trastorno metabólico crónico caracterizado por hiperglucemia, resistencia a la insulina (RI) y metabolismo anormal de ácidos grasos en el que se ha implicado el receptor CD36 en la disregulación de la glucosa y los lípidos. Objetivo: evaluar la contribución del polimorfismo CD36 rs3211938 al perfil metabólico en individuos mestizos mexicanos con DMT2 del occidente de México. Métodos: se incluyeron 115 individuos clasificados en adultos sin DMT2 (NDMT2) y pacientes con DMT2. El polimorfismo CD36 rs3211938 se identificó mediante PCR-RFLP. Las mediciones antropométricas y metabólicas se realizaron mediante métodos de rutina y la insulina y las LDL-oxidadas (LDL-ox) se midieron por ELISA. Resultados: las distribuciones de los genotipos entre los pacientes NDMT2 y DMT2 fueron diferentes (p0,001), así como la frecuencia alélica (p = 0,002). Los individuos NDMT2 portadores del genotipo TG mostraron niveles más bajos de insulina basal e índice HOMA-IR en comparación con los portadores del genotipo TT (p0,05 y p0,05, respectivamente). En el grupo DMT2, los portadores del genotipo TG presentaron valores elevados de índice de masa corporal (IMC), índice cintura-cadera (ICC) y peso (p = 0,001; p0,05 y p0,05, respectivamente) y niveles más altos de glucosa basal, HDL-colesterol, LDL-ox y HOMA-IR (p0,001; p0,001; p0,001 y p = 0,001, respectivamente) en comparación con los portadores del genotipo TT. Conclusión: el genotipo TG del polimorfismo CD36 rs3211938 se asocia a altos niveles de glucosa, ox-LDL, HDL-colesterol y RI, y a aumentos del IMC en los pacientes mestizos mexicanos con DMT2 del occidente de México.

Congenital Disorders of Glycosylation (CDG) are scarcely reported from Latin America. We here report on a Mexican mestizo with a multi-systemic syndrome including neurological involvement and a type I transferrin (Tf) isoelectric focusing (IEF) pattern. Clinical exome sequencing (CES) showed known compound missense variants in PMM2 c.422G > A (p.R141H) and c.395 T > C (p.I132T), coding for the phosphomanomutase 2 (PMM2). PMM2 catalyzes the conversion of mannose-6-P to mannose-1-P required for the synthesis of GDP-Man and Dol-P-Man, donor substrates for glycosylation reactions. This is the third reported Mexican CDG patient and the first with PMM2-CDG. PMM2 has been recently identified as one of the top 10 genes carrying pathogenic variants in a Mexican population cohort.

Background: Genome-wide association studies (GWAS) for colorectal cancer (CRC) have detected high-risk genetic variants associated with CRC in several ethnic groups, but Latin American communities are still underrepresented. The aim was to identify variants related to CRC in an admixed Latin American population. Methods: The study was performed in 831 cases and 881 controls from Mexico, who were genotyped for 1,006,703 autosomal SNPs. Logistic regression was carried out including covariants, such as sex, age and genetic ancestry. Lastly, we performed a sequence-kernel association test (SKAT) to consider the joint effect of several SNPs lying in genes.Results: Eight chromosomal regions reached genome-wide significance level ( p < 5×10 -8 ): 1p36.22, 1p31.1, 1q42.13, 6p22, 7p14.1, 12q24.32, 16q12.2 and 21q22.2 and 63 variants reached borderline statistical significance ( p < 1×10 − 6 ). SKAT analysis detected 13 loci associated with CRC, none of them previously associated with CRC. Conclusions: We found 8 SNPs and 13 loci associated with CRC. These signals may contribute to enrich the panoply of genes involved with CRC. Further analyses remain to be done to validate the associations in other Latin American populations. This study highlights the importance of conducting GWAS in poorly explored admixed populations.

Background Mexican mestizo population has a pluriethnic mixture of Amerindian, European and African ancestry, predominant in most Latin American countries. Until now, there are no reports about hair characteristics in this population, necessary to define normal values, for hair diseases evaluation and comparison among other ethnic groups. Methods The VivoSight® swept-source multibeam optical coherence tomography system was used to evaluate hair diameter and shape in 30 females. Three hair samples from each volunteer were measured transversely along three distances, generating nine cross-sectional images, two measurements per image and 18 measurements per patient for a total of 540 diameter measurements. Results Minimum hair diameter (n = 540) was 0.06 mm while maximum was 0.14 mm. Mean diameter was 0.10 ± 0.01 mm as compared with Asian hair, which ranges from 0.08 mm to 0.12 mm. On morphological analysis, Mexican Mestizo hair tends to have a round shape with homogenous diameters, resembling Caucasian and Asian hair. Conclusion Mexican hair is similar to Asian hair in diameter and shape and can be classified as 'thick' hair, which make it more resistant and with more volume. Cosmetic products intended to improve hair care in this population must to consider this characteristic.

The rec(8)dup(8q)inv(8)(p23.1q22.1) chromosome associated with San Luis Valley Syndrome (SLVS OMIM 179613) is usually diagnosed in Hispanic patients from the USA Southwest where a founder carrier Spaniard lived around 1800 [1, 2]. This rec(8) has an 8q duplication of 47.90 Mb and an 8p deletion of 11.65 Mb [3, 4]. Excluding two de novo rec(8)dup q chromosomes characterized only by G-bands and included in a recent compilation [5], cytogenomic analyses identified nine comparable de novo der(8)dup q/del p chromosomes with or without a simultaneous 8p gain. We describe a Mexican mestizo girl with a de novo SLVS-like der(8) but with a concomitant 8p22p23.1 duplication

O6-Methylguanine-DNA methyltransferase (MGMT) is an enzyme that repairs the DNA damage caused by the tobacco habit, and low activity of this enzyme has been associated with a risk of lung cancer (L...

Individuals who suffer from spinal muscular atrophy (SMA) exhibit progressive muscle weakness that frequently results in mortality in the most severe forms of the disease. In 98% of cases, there is a homozygous deletion of the survival of motor neuron 1 (SMN1) gene, and both parents carry the same heterozygous genetic abnormality in the majority of cases. Various population studies have been conducted to estimate the frequency of carriers and thereby identify the communities or countries in which children are at a high risk of being affected by SMA. However, the prevalence of SMA in Mexican populations has not yet been established. In the present pilot study, the frequency of the heterozygous deletion of the SMN1 gene was determined in two groups from northeastern (n=287) and central (n=133) Mexican Mestizo populations and compared with other ethnic populations. Amplification refractory mutation system polymerase chain reaction analysis yielded a disease carrier frequency of 11/420 (2.62%) healthy individuals, comprising 9/287 (3.14%) northeastern and 2/133 (1.5%) central Mexican individuals. In summary, no significant differences were identified between the northeastern and central populations of Mexico and other ethnic populations, with the exception of the general worldwide Hispanic population, which exhibited the lowest carrier frequency of 8/1,030. The results of the present study may be used to improve the evaluation procedure, and appear to justify further studies involving larger sample populations.

Background To determine the activity of antithrombin (AT), protein C (PC), and protein S (PS), as well as the frequency of deficiencies of these proteins in a population of healthy Mexican mestizo blood donors. Methods AT, PC, and PS were determined from 1,502 plasma samples of healthy blood donors by using commercial kits in a coagulometer 4 STA (Diagnostica Stago, Asnieres, France). Results A total of 741 women and 761 men were under study. They were divided into age range groups (18–24, 25–34, 35–44, 45–54, and 55–64 years). Activity of AT, PC, and PS was determined. For AT, activity values were specific for each age group according to gender when it had to do with PS, as well as when PC was determined. Frequencies of AT, PC, PS, and activated PC resistance activity deficiencies were obtained from reference levels (RLs) and average levels of this study. Differences were found between both frequencies for AT, PC, and PS, and the average levels obtained were used in this study. The frequencies of the activity deficiencies obtained through the values gotten in this population were: AT, 0.6%; PC, 1.06% (which is higher than the one obtained using the RLs described by commercial kits 0.33% and 0.66%, respectively); and PS, 1% (which is less than 4.5%). Conclusions It is necessary to know the characteristics and biological behavior of the coagulation proteins in the Mexican population because the RLs used have been established for populations that are genetically different.

Coumarins are widely prescribed worldwide, and in Mexico acenocumarol is the preferred form. It is well known that despite its efficacy, coumarins show a high variability for dose requirements. We investigated the pharmacogenetic variation of 110 genes in patients receiving acenocumarol using a targeted NGS approach. We report relevant population differentiation for variants on CYP2C8, CYP2C19, CYP4F11, CYP4F2, PROS, and GGCX, VKORC1, CYP2C18, NQO1. A higher proportion of novel-to-known variants for 10 genes was identified on 41 core pharmacogenomics genes related to the PK (29), PD (3), of coumarins, and coagulation proteins (9) including, CYP1A1, CYP3A4, CYP3A5, and F8, and a low proportion of novel-to-known variants on CYP2E1, VKORC1, and SULT1A1/2. Using a Bayesian approach, we identified variants influencing acenocumarol dosing on, VKORC1 (2), SULT1A1 (1), and CYP2D8P (1) explaining 40–55% of dose variability. A collection of pharmacogenetic variation on 110 genes related to the PK/PD of coumarins is also presented. Our results offer an initial insight into the use of a targeted NGS approach in the pharmacogenomics of coumarins in Mexican Mestizos.

Aim: In previous CYP2D6 genotyping studies in Mexican–Amerindians a very low frequency of poor metabolizers (PMs) has been reported. Moreover, ultrarapid metabolizers (UMs) status has only been analyzed in some groups from Northern Mexico. Materials & methods: In the present study we evaluated the hypothesis of low frequency of PMs in Mexican–Amerindians in Southern Mexican populations from Chiapas (Lacandones [ML] vs Mestizos [MM]). The frequency of UMs is also reported. CYP2D6 alleles *2, *3, *4, *5, *6, *10, *17, *35 and *41 and copy number variations were analyzed in 154 ML and 100 MM healthy volunteers. Results: The PM frequency was 0% in MLs and 1% in MMs, and for UMs was 2.6% in MLs and 3% in MMs. Conclusion: The present data support previous findings reporting a very low frequency of CYP2D6 PMs in Mexican–Amerindians. Furthermore, the predicted UM phenotype in both MMs and MLs was lower than those reported for most Mexican populations. Original submitted 16 May 2014; Revision submitted 26 September 2014

Summary Turner syndrome (TS) is one of the most common sexual chromosome abnormalities and is clearly associated with an increased risk of autoimmune diseases, particularly thyroid disease and coeliac disease (CD). Single-nucleotide polymorphism analyses have been shown to provide correlative evidence that specific genes are associated with autoimmune disease. Our aim was to study the functional polymorphic variants of PTPN22 and ZFAT in relation to thyroid disease and those of MYO9B in relation to CD. A cross-sectional comparative analysis was performed on Mexican mestizo patients with TS and age-matched healthy females. Our data showed that PTPN22 C1858T (considered a risk variant) is not associated with TS (X2 = 3.50, p = .61, and OR = 0.33 [95% CI = 0.10–1.10]). Also, ZFAT was not associated with TS (X2 = 1.2, p = .28, and OR = 1.22 [95% CI = 0.84–1.79]). However, for the first time, rs2305767 MYO9B was revealed to have a strong association with TS (X2 = 58.6, p = .0001, and OR = 10.44 [95% C = 5.51–19.80]), supporting a high level of predisposition to CD among TS patients. This report addresses additional data regarding the polymorphic variants associated with autoimmune disease, one of the most common complications in TS.

El labio leporino no sindromico con o sin paladar hendido es un defecto congenito craneofacial comun que afecta aproximadamente a 1 de cada 1.000 nacidos vivos en todo el mundo. Entre los genes asociados con esta condicion se encuentran IRF6, MSX1, TGFA, TGFB3 y PVRL1, aunque solo se ha informado de la asociacion de IRF6 [Dixon et al., 2011]. Recientemente, se informo de una fuerte asociacion genetica de una region de 640 kb de 8q24 a NS CL - P [Birnbaum et al., 2009]. Hasta la fecha, ha habido poca informacion sobre los factores ambientales y geneticos asociados con NS CL - P en poblaciones mestizas mexicanas. Por consiguiente, se realizo un estudio de casos y controles que analizo la asociacion de 17 variantes de cinco genes candidatos (IRF6, MSX1, TGFA, TGFB3 y PVRL1) y la region cromosomica 8q24, con NS CL - P, utilizando ambos analisis de asociacion simple y haplotipo . Tambien se analizaron los efectos de las interacciones entre todas las variantes geneticas y la ingesta materna de acido folico en el riesgo de NS CL - P.

Systemic sclerosis (SSc) shows variable clinical expression among different ethnic groups. Herein, we describe the clinical features, prevalence of organ involvement, and autoantibody profile in Mexican Mestizo SSc patients and we compare them with patients from other ethnic groups.We included 139 SSc patients. They underwent clinical evaluation and were tested for antinuclear antibodies (ANA), anticentromere antibodies (ACA), anti-topoisomerase I, anti-RNA polymerase III, anti-U1 RNP, anti-U3 RNP, anti-U11/U12 RNP, anti-Th/To, anti-PM-Scl, anti-Ku, antinucleosome, anti-double-stranded DNA (dsDNA), anti-Sm, anti-SSA, and anti-SSB antibodies. Female predominance (93.5%) was noted; 56.8% of patients had limited cutaneous SSc; 91% had peripheral vascular involvement; 70% had joint involvement; 27% had musculoskeletal damage; 66% had gastrointestinal involvement; 41% had interstitial lung disease; 32% had pulmonary arterial hypertension (PAH); 11% had cardiac involvement; and in 1.4% renal involvement was observed. Our patients showed lower frequency of renal crisis and higher frequency of PAH than patients from other ethnic groups; also they showed higher frequency of ACA than Japanese and African American patients, higher frequency of anti-topoisomerase I than Caucasian and African American patients, higher frequency of anti-PM-Scl and anti-Ku and lower frequency of anti-RNA Pol III than the other ethnic groups. High frequencies of antinucleosome (41%) and anti-dsDNA (63%) were identified. SSc-specific autoantibody frequencies are different in our patients and in those from other ethnic groups; associations of autoantibodies with clinical manifestations are confirmed in our patients. Ethnicity and the interaction of gene and environmental factors may influence the clinical picture and autoantibody profile in SSc patients.

Genetic data from 17 autosomal short tandem repeat (STR) loci found in the Powerplex® ESX 17 System (Promega, Madison, WI, USA) was evaluated in 162 unrelated Mexican Mestizo individuals from Mexico City. Allele frequencies and forensic parameters were estimated for the 17 STRs. All loci analyzed were in Hardy-Weinberg equilibrium in the studied population and showed not any signs of linkage between loci. The combined power of discrimination and the power of exclusion for the 16 aSTRs studied were 1–2.56409·10−19 and 99.999938 %, respectively. Genetic distances reveal a close relationship within different populations of Mexican Mestizos. The obtained data might be useful for population genetics research and for individual identification and paternity testing in forensic science.

SUMMARY Aim: The DD genotype of angiotensin-converting enzyme (ACE) has been suggested as a major contributor of diabetic nephropathy in several populations. The purpose of the present study was to determine whether micro/macroalbuminuria is associated with ACE insertion/deletion (I/D) polymorphism in Mexican Mestizos with type 2 diabetes mellitus. Methods: A total of 435 patients with type 2 diabetes mellitus, of whom 233 had albuminuria, were characterized for the ACE I/D polymorphism by the polymerase chain reaction method. Results: Clinical and biochemical characteristics and frequencies according to DD, ID and II genotypes in patients with and without albuminuria showed no significant differences. However, only females with micro/macroalbuminuria showed higher frequency of a DD genotype than those without albuminuria (27.9%, 21.2% and 10.5%, respectively; P ≤ 0.044). In addition, female patients with macroalbuminuria without dialysis showed no significant differences with patients undergoing dialysis. Conclusion: The ACE DD genotype is a risk factor for the development of renal disease in Mexican Mestizo females with type 2 diabetes, indicating a possible DD genotype-associated sex effect in renal disease.

The aim of the present study was to reevaluate the distribution of HLA antigens in Mexican Mestizos since, in our previous report, very few specificities were explored for this population. The Mestizos are primarly a mixture of Caucasians (Spaniards) and Mexican Indians and account at the present time for about 95% of the total Mexican population. A and B antigens were typed on isolated cells using a microlymphocytotoxicity technique. Antigen, gene and haplotype frequencies were calculated including the significance for delta values. The results clearly showed that the HLA distribution differs from other ethnic groups and the predominant antigens are A2, A9, B5, Bw35 and B40, but the general pattern clearly shows the participation in genetical composition of Spanish and Mexican Indian backgrounds. The most frequent haplotypes were A2-B5, A9-Bw35, A9-B40 and A2-B40, which are also the most common in some Mongoloid populations.

Cytochrome 1A1 (CYP1A1), glutathione transferase M1 (GSTM1), and glutathione transferase T1 (GSTT1) catalyze the bioactivation and detoxification of a wide variety of xenobiotic compounds that are mutagenic and/or carcinogenic (e.g., polycyclic aromatic hydrocarbons). Genetic polymorphisms of these metabolizing enzymes have been shown to affect individual susceptibility to environmental carcinogenic compounds. Although several studies have been published on the relationship between CYP1A1*2C, GSTM1*0, or GSTT1*0 polymorphism and cancer, not all findings can be extrapolated to other populations because of interethnic variability. Here, we investigate the frequency of CYP1A1*2C, GSTM1*0, or GSTT1*0 in a sample of Mexican Mestizos. We find that the frequency of GSTM1*0 is 0.335, that of GSTT1*0 is 0.121, and that of GSTM1*0 + GSTT1*0 is 0.023. The frequency of CYP1A1*2C is 0.54. Similitude analysis sets the Latin American populations in a common cluster near the Asian population, suggesting that the CYP1A1*2C polymorphism may have originated from this population and suffered a founder effect in the American population. Analysis of CYP1A1*2C, GSTM1*0, and GSTT1*0 haplotypes reveals that 35% of the population has some combination of risk genotypes. Taken together, these results point to a high susceptibility of the Mexican Mestizo population to the effects of environmental carcinogens.

A population sample from Sao Tome e Principe (West Africa) was screened for the G6PD-deficient variants A– (376G/202A), Betica (376G/968C), and Santa Maria (376G/542T). G6PD locus haplotype diversity was also investigated using six intragenic RFLPs (FokI, PvuII, BspHI, PstI, BclI, NlaIII) and a (CTT)n microsatellite 18.61 kb within the G6PD locus. The estimated frequencies of the G6PD*B normal allele, the G6PD*A variant (376G), and the G6PD*A– allele were 0.698, 0.194, and 0.108, respectively. G6PD variants Betica and Santa Maria were not found. Similar levels of microsatellite diversity were found on variants G6PD*B and G6PD*A (H= 0.61 and 0.68, respectively), indicating a similar age for both alleles. All G6PD*A– alleles share the RFLP-microsatellite haplotype ++–+–+/195, the same haplotype described in nearly all the *A– alleles from sub-Saharan, Mexican Mestizo, and Portuguese populations, consistent with a single and recent origin of the G202A mutation on this *A haplotype.

To investigate the origin of von Willebrand disease in Mexican Mestizo population, we analyzed exons 18, 19, 20, 28, 45, and 52 of the VWF gene from 34 Mexican Mestizo index cases, 28 of them affected but not related, using DNA amplification by polymerase chain reaction and direct sequencing. We found three novel mutations: E1447Q in one patient with type 1; P2781S in one patient with type 2M; and P812L in another type 1/2N patient. These mutations were not found in 100 normal alleles. Moreover, we found other mutations previously reported in the literature; one of them (G1609R) was the most frequent (6/28) in patients with VWD type 2A. This is the first molecular study in a Mexican group that has a particular mixture of Indigenous, Caucasian, and African genes.

Genotyping for the G6PD (AC)n and (CTT)n microsatellites in a sample of 58 Mexican Mestizos with common G6PD African variants was carried out. The second mutation that defines to the variants G6PD A − 202A/376G , G6PD Santamaria 376G/542T and G6PD A − 376G/968C very probably occurred on G6PD A 376G chromosomes with the compound haplotypes, intragenic silent polymorphisms and microsatellites, Pvu-II/Pst-I/Bcl-I/Nla-III/(AC)n/(CTT)n: +/+/−/+/166 bp/195 bp, −/+/−/+/166 bp/201 bp, and −/+/−/+/166 bp/204 bp respectively. The structure of the repeat sequences for the AC-166 bp allele in the 3 variants was (TA)5(AA)1(TA)9(CA)10 whereas the repeat sequences for the CTT-195 bp, CTT-201 bp and CTT-204 bp alleles were (CTT)11(ATT)6, (CTT)7(ATT)12 and (CTT)7(ATT)13 in the first, second and third variants respectively. Genotyping for the G6PD microsatellites can be a useful tool with several applications.

Background and Aims: The variable that most strongly predicts the degree of nicotine addiction is the quantity of cigarettes smoked per day. A variety of studies have reported a high heritability of nicotine dependence. However, no data exist for any population of Latin Americans, who exhibit different degrees of racial mixing. Therefore, the present analytic, cross-sectional study was conducted. Methods: Smokers were included (n=515) and classified based on their consumption of cigarettes per day (cpd) as: light smokers (1-10 cpd, LS, n=328) and heavy smokers (≥20 cpd, HS, n=187). Additionally a group of non-smokers (NS, n=192), who were clinically healthy volunteers, were included. A genotyping microarray measuring 384 SNPs was employed in the CHRNA2 to CHRNA7, CHRNA10, CHRNB2 to CHRNB4 and NRXN1 genes, including 37 informative ancestry markers. The Eigensoft, Haploview, PLINK, EPIDAT v3.1, SPSSv15, and Epi-info v7.0.3 software programs were used for this analysis. Results: Twenty-one SNPs in six genes were identified with statistically significant differences; NRXN1 and CHRNA5 are the genes with the most associated SNPs (7 and 6, respectively). Comparing LS vs . NS, the p-values were found to be between 7.85E-03 and 5.84E-07, and the OR values were between 2.13 and 4.28; in HS vs . NS, these values ranged from 8.23E-04 to 1.45E-10, with the lowest OR being 2.88 and the highest being 7.99. Conclusions: In the Mexican Mestizo population, smoking and, in particular, a greater consumption of cigarettes are influenced by polymorphisms in genes NRXN1 , CHRNA3 , CHRNA5 , and CHRNB4 .

The aim of this study was to determine the frequency of α-globin gene mutations in three groups of Mexican unrelated individuals. The first two groups were normal and sickle cell trait individuals from the Costa Chica region, a place with a 12.8% frequency of HbS carriers, and the third group comprised of Mexican mestizo patients with β-thalassemia. We searched for −α 3.7 and −α 4.2 α + -thalassemia deletion alleles, as well as the ααα anti3.7 triplication through long-gap PCR. The alleles −α 3.7 and ααα anti3.7 were found in the heterozygote state only; 19% of the normal subjects had the −α 3.7 allele, and 2% showed the ααα anti3.7 allele. In individuals with the sickle cell trait, 17% had the −α 3.7 deletion, and the ααα anti3.7 triplication was observed in 3% of these individuals. We revealed that 16% of the subjects with β-thalassemia showed the −α 3.7 deletion and 28% the ααα anti3.7 triplication. The −α 4.2 deletion was not detected in any individual. The frequency of the −α 3.7 allele was roughly the same in the three groups studied; this can be explained by the fact that the three groups have common genes from Africa and the Mediterranean, where a high prevalence of α + -thalassemia has been observed. To our knowledge, the frequency of ααα anti3.7 triplication observed in the Mexican β-thalassemia patients is the highest reported. As the −α 3.7 and ααα anti3.7 alleles are very common in our selected populations, we believe that there is a need to investigate systematically the α-globin gene mutations in all hemoglobinopathies in the Mexican population.

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

To investigate the origin of the beta(A) and beta(S) genes in a Mexican population with African roots and a high frequency of hemoglobin S, we analyzed 467 individuals (288 unrelated) from different towns in the states of Guerrero and Oaxaca in the Costa Chica region. The frequency of the sickle-cell trait was 12.8%, which may represent a public health problem. The frequencies of the beta-haplotypes were determined from 350 nonrelated chromosomes (313 beta(A) and 37 beta(S)). We observed 15 different beta(A) haplotypes, the most common of which were haplotypes 1 (48.9%), 2 (13.4%), and 3 (13.4%). The calculation of pairwise distributions and Nei's genetic distance analysis using 32 worldwide populations showed that the beta(A) genes are more closely related to those of Mexican Mestizos and North Africans. Bantu and Benin haplotypes and haplotype 9 were related to the beta(S) genes, with frequencies of 78.8, 18.2, and 3.0%, respectively. Comparison of these haplotypes with 17 other populations revealed a high similitude with the population of the Central African Republic. These data suggest distinct origins for the beta(A) and beta(S) genes in Mexican individuals from the Costa Chica region.

This study compares genetic polymorphisms at the D1S80 and HLA-DQA1 loci in three Mexican Mestizo populations from three large states (Nuevo Leon, Jalisco, and the Federal District). Allele frequency distributions are relatively homogenous in the three samples; only the Federal District population shows minor differences of the HLA-DQA1 allele frequencies compared with the other two. In terms of genetic composition, these Mestizo populations show evidence of admixture with predominantly Spanish-European (50-60%) and Amerindian (37-49%) contributions; the African contribution (1-3%) is minor. Together with the observation that in Nuevo Leon, the admixture estimates based on D1S80 and HLA-DQA1, are virtually the same as those reported earlier from blood group loci, suggests that DNA markers, such as D1S80 and HLA-DQA1 are useful for examining genetic homogeneity/heterogeneity across Mestizo populations of Mexico. The inverse relationship of the proportion of gene diversity due to population differences (Gst) to within population gene diversity (Hs) is also consistent with theoretical predictions, supporting the use of these markers for population genetics studies. Am. J. Hum. Biol. 14:257-263, 2002. © 2002 Wiley-Liss, Inc.

ABSTRACT Since no data have previously been reported concerning both the (TA) n polymorphism at the promoter of the UGT1A1 gene in the Mexican population and the use of single-strand conformation polymorphism (SSCP) for the detection of such polymorphism, genotyping by SSCP in 375 G-6-PD normal (Group A) and 81 G-6-PD-deficient (Group B) mestizos belonging to 14 states was carried out. Allele frequencies for (TA) 6 and (TA) 7 repeats were 0.654 and 0.334, respectively, in Group A and 0.685 and 0.315 in Group B; in the former group, the (TA) 5 allele was also observed with a frequency of 0.012. The frequencies of the genotype (TA) 7 /(TA) 7 were 10.1% (Group A) and 8.6% (Group B). The (TA) 7 /(TA) 8 genotype was also observed in a patient with unconjugated hyperbilirubinemia. Due to the importance of its potential medical implications, the observed high frequency (10%) of the (TA) 7 /(TA) 7 genotype is stressed. Genotyping by SSCP of the (TA) n polymorphism is an adequate methodological option.

Aim Patterns of genetic variation within and between populations have provided novel insights into the origin and history of humans. STRs are versatile and informative markers that facilitated a great understanding of the diversity present in natural populations, being a common tool in forensics, paternity and anthropological studies. Data collection for such studies is conducted based on many groups. Mexican Mestizos are of mixed descent and are the result of admixture between the Indigenous people of Asian ancestry inhabiting the country, different Europeans, and to a lesser extent, Africans. We intended to describe the pattern of 24 STRs in Mexican Mestizos for the above purposes. Methods STRs were typed in 817 Mestizo adults, born in Mexico, (55.9% males and 44.1% females), by using PowerPlex21, GenePrint 24 (Promega), Global filer and Identifiler (Thermofisher Scientific) systems. We investigated 24 autosomal STRs in genomic DNAs. The STRs were run in a 3500 Sequencer and the DNA fragment analysis was done with the Gene Mapper ID-X v1.4 software. Allele frequency(AF) was compared with other studies done for forensics. Linkage disequilibrium(Δ), hardy–Weinberg equilibrium (HWE), Power of Exclusion (PE), Power of Discrimination (PD) and R Pearson value were determined. Results A total of 347 alleles at the 24 STR loci were found with corresponding AF ranging between 0.045 and 52.66. These STRs are highly polymorphic being the most diverse FGA, D18551, PentaE, D21511, SE33 and D6S1043 (31–18 alleles). The most frequent alleles >25% were; 10 at D2S441; 11 at D5S818; 11 at D7S820; 14 at D6S1043; 14 at D19S433; 19 & 20 at D12S391; 10 at D7S820. These were compared with data of Central Mexico and from 13 CODIS from Latin American and Caribbeans. Conclusions The 24 autosomal STR loci provide highly informative polymorphic data, since the R Pearson value = 0.985 (SD = 0.02). Some alleles were in Δ, meaning they are not in random association in 13/24 STRs (D16S539, D12S391, D19S433, PentaD, FGA, TH1, TPOX, D18S51, PentaE, D21S11, D18S51, D3S1358, CSF1PO). The PD = up to 0.974, showing high heterozygosity and low probability of finding two individuals with the same genotypes and PE = 0.947 shows the power of detecting variation. STRs may also be used together, since many are in Δ, to solve deficient kinship cases or cases with mutations.

Mexican Mestizos, who are the result of the admixture of Spanish, Indian, and Black genes, were analyzed for different systems. Three populations from geographical distinct areas were studied: the north (State of Nuevo Leon ), the center (State of Guanajuato), and the highlands (mainly Mexico City). Ten blood group systems (N = 229), STRs (N = 107), HLA-A*, B*, C* (N = 116-167), and DRB1, DQA1, and DQB1 (N = 40, 101, 160, respectively) were analyzed in the samples of the highlands. The three groups cluster together in the same branch: Mestizos from Venezuela, Mediterranean and Jews close to the cluster of Orientals, followed by Amerindians. All markers demonstrate that Indian genes are strongly represented in the highlands: Di(a), O, D(-)(+), s, A*0201, *0206, B*1539 (*1541), *3902, *3905, *3512, *3517, *4002, *4005, Cw*0801, *0304, *0401 among others. Cw*0501, *1203, *1204, and *1601 are of White ancestry. The most frequent haplotypes *0407-*03011-*0302 and *0802-*0401-*0402 are of Indian descent as well. The center and mainly the north show a more Caucasian and Semitic profile. The results demonstrate the high variability resulting from interethnic admixture, suggesting that this mechanism is the main factor responsible for the large diversity found in urban populations.

ABSTRACT In a screening for glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in 1985 unrelated male subjects from the general population (Groups A and B) belonging to four states of the Pacific coast, 21 G-6-PD-deficient subjects were detected. Screening for mutations at the G-6-PD gene by PCR-restriction enzyme in these 21 G-6-PD-deficient subjects as well as in 14 G-6-PD-deficient patients with hemolytic anemia belonging to several states of Mexico showed two common G-6-PD variants: G-6-PD A- 202A/376G (19 cases) and G-6-PD A- 376G/968C (9 cases). In 7 individuals the mutations responsible for the enzyme deficiency remain to be determined. Furthermore, four silent polymorphic sites at the G-6-PD gene ( Pvu II, Pst I, 1311, and Nla III) were investigated in the 28 individuals with G-6-PD A- variants and in 137 G-6-PD normal subjects. As expected, only 10 different haplotypes were observed. To date, in our project aiming to determine the molecular basis of G-6-PD deficiency in Mexico, 60 unrelated G-6-PD-deficient Mexican males—25 in previous studies and 35 in the present work—have been studied. More than 75% of these individuals are from states of the Pacific coast (Sinaloa, Nayarit, Jalisco, Michoacan, Guerrero, Oaxaca, and Chiapas). The results show that although G-6-PD deficiency is heterogeneous at the DNA level in Mexico, only three polymorphic variants have been observed: G-6-PD A- 202A/376G (36 cases), G-6-PD A- 376G/968C (13 cases), and G-6-PD Seattle 844C (2 cases). G-6-PD A- variants are relatively distributed homogeneously and both variants explain 82% of the overall prevalence of G-6-PD deficiency. The variant G-6-PD A- 202A/376G represents 73% of the G-6-PD A- alleles. Our data also show that the variant G-6-PD A- 376G/968C —which has been observed in Mexico in the context of two different haplotypes—is more common than previously supposed. The three polymorphic variants that we observed in Mexico are on the same haplotypes as found in subjects from Africa, the Canary Islands, and Spain.

Human leukocyte antigen-B*9550 is a novel allele identified in a Mexican Mestizo bone marrow donor from Veracruz.

Twenty-five individuals were studied from four unrelated Mexican Mestizo families with Hb D-Los Angeles. We observed five compound heterozygotes: four for Hb S and Hb D, and one for Hb D and beta-thalassemia (beta(0) 39 nonsense mutation); 16 heterozygotes: four for Hb S, seven for Hb D, and five for beta-thalassemia, while the remaining four were normal. The four Hb S/Hb D patients had severe hemolytic anemia, while in the Hb D/beta-thalassemia patient, the anemia was similar to that of a beta-thalassemia heterozygote; therefore, Hb D is clinically harmful when it is associated with Hb S. The beta(S) chromosomes were associated with the Benin haplotype in two families and Bantu in one family, while the beta(D) and beta(0) 39 mutations were associated with haplotype 1 [+ - - - - + +]. The Bantu and Benin haplotypes have been found with high frequency in Hb S individuals from the East Coast and Northwestern Mexico. The beta(D) chromosomes from Italy were also shown to be associated with haplotype 1, the most frequently observed haplotype in the world; there are no haplotype studies on beta(D) chromosomes from India or China where Hb D-Los Angeles is most common. Thus, the true origin of this mutation observed in these Mestizo families remains to be elucidated.

Background In some Caucasian populations it has been found that the C282Y hemochromatosis (HFE) gene mutation is a risk factor for the development of leukemia and other malignancies. Methods In a group of 50 Mexican mestizo patients and 153 normal controls, the HFE gene mutations H63D and C282Y were studied by means of ARMS-PCR. Results In the group of patients with leukemia we found a heterozygote for the C282Y mutation, seven heterozygotes for the H63D mutation, a double heterozygote for the H63D / C282Y mutation and 41 normal homozygotes. These data are not different from those observed in normal controls, where the allele frequencies were 0.062 and 0.013 for the H63D and C282Y HFE gene mutations, respectively. Conclusions These HFE gene mutations are not risk factors for the development of leukemia in Mexican mestizos.

UDP-glucuronosyltransferase 1A4 (UGT1A4) is a phase II drug-metabolizing enzyme that catalyzes the glucuronidation of many clinically-important drugs. Interethnic differences in the genetic polymorphism of UGT1A4 have been reported; however, there is no information in Mexican Mestizos (MMs) and Spaniards (SPs). Furthermore, MM is an admixed population with 26 % of Caucasian genes mainly from Spain. Therefore, this study aimed to investigate the potential differences between 318 SPs and 248 MMs healthy individuals regarding UGT1A4*1b, UGT1A4*2 and UGT1A4*3 alleles and to compare the observed frequencies with those previously reported in different populations. The allelic frequencies of the three UGT1A4 polymorphisms showed interethnic differences between MMs and SPs (p < 0.05). The analyzed SNPs variants in this genetic region were not in linkage disequilibrium (LD) for the MM population, suggesting that these mutations have arisen independently in the same genetic background. In contrast, UGT1A4*2 and UGT1A4*3 were in LD in the SP population. Comparison of present data with other in different ethnic groups revealed that the frequencies of UGT1A4*2 and UGT1A4*3 in SP were similar to other Caucasians and higher than in Asians, whereas in MMs were lower than in Caucasians and higher than in Asians only for UGT1A4*2. Present results could be helpful to improve the use of UGT1A4 drug substrates in order to adjust them to the ethnic background of a given population, specifically for Hispanics.

The concept of shared autoimmunity comprises various forms of disease: rheumatic diseases in several members of the same family, the coincidence of autoimmune rheumatic with non-rheumatic diseases in relatives of patients, the presence of autoantibodies in healthy relatives of autoimmune disease patients, and the development of two or more autoimmune rheumatic diseases in one patient, the so-called overlap syndromes. The genetic and environmental factors that lead to these phenomena interact in a complex fashion and influence the distinct phenotypic characteristics of each patient. In a previous case series, we described 23 Mexican Mestizo patients with overlap syndromes. Interestingly, rhupus tends to develop sequentially while sclerodermatomyositis tends to appear simultaneously. The clinical course of the other overlap syndromes is rather aggressive, although clinical manifestations respond to standard treatment. The second and/or third disease appears while the first one is still active, even with adequate treatment. The distinct course of overlap syndromes may be partially explained by the interplay of environmental factors with genes that predispose to autoimmunity in general and to manifestations of specific diseases. The analyses of genes that will help understand the pathophysiology of these diseases include several MHC complex genes, cytokines, AIRE, and PDCD1 amongst others.

Background There is strong evidence that an individual's genetic background is an important predisposing factor to longevity. In the present study we analysed the frequency of HLA class I, class II, as well as the TNF-α -308 polymorphism that may be related to an increased life span in Mexican Mestizo healthy elders. Results HLA typing was performed by polymerase chain reaction sequence specific oligonucleotide (PCR SSO) reverse dot blot. The TNF-α -308 polymorphism was assessed by PCR restriction fragment length polymorphism. A significant increased frequency of HLA-DRB1*11 was found in elderly women whereas this allele was not present in elderly males. The TNF2 allele was also increased in the elder group when compared to young controls. The frequencies of the remaining alleles tested were not statistically different among groups. Conclusion These data suggest an ethnicity independent tendency of HLA-DRB1*11 in elder females to increase life span and a possible role of the TNF2 allele with the successful remodelling of senescent immune system.

Apolipoprotein E (apoE) genotypes were determined in 165 Saudis. The prevalence of genotype, E3/E3, E3/E4 and E4/E4 was found to be 71, 27 and 2% respectively. The E3/E3 was the most prevalent genotype among the Saudis followed by E3/E4. However, other genotypes E2/E2, E2/E3 and E2/E4 were absent showing the absence of E2 allele in the test population. The high frequencies of the E3 allele (0.845) and E3/E3 genotype (0.71) and absence of E2 allele in Saudis under study are similar to those reported earlier for Native Americans, Mexican-Americans, Mayans, Cayapa, Mazatecan Indians and Mexican Mestizos populations.

The A*29:47 allele was identified in a Mexican Mestizo unrelated bone marrow donor from the state of Hidalgo.