FNDC5/Irisin polymorphisms are associated with osteopenia in postmenopausal Mayan-Mestizo women.

OBJECTIVE: This study aimed to analyze the association between rs3480 and rs16835198 of FNDC5/Irisin and their haplotypes with variations in bone mineral density (BMD) and osteopenia/osteoporosis in postmenopausal Mayan-Mestizo women. METHODS: We studied 547 postmenopausal women of Maya-Mestizo origin. BMD was measured in the lumbar spine and total hip by dual-energy X-ray absorptiometry. DNA was obtained from blood leukocytes. rs3480 and rs16835198 of FNDC5/Irisin were studied using real-time PCR allelic discrimination. Differences between the means of BMD according to genotype were analyzed with covariance. Allele frequency differences were assessed by χ2 and logistic regression was used to test for associations. Pairwise linkage disequilibrium between polymorphisms was calculated by direct correlation r2, and haplotype analysis was conducted. RESULTS: Under a recessive model, we observed a significant association of rs3480 with the presence of osteopenia at the total hip and femoral neck (p = 0.008 and p = 0.003, respectively). For rs16835198, we found an association with osteopenia at the total hip and femoral neck in a dominant model (p = 0.043 and p = 0.009, respectively). CONCLUSIONS: We found an association of rs3480 with risk to present osteopenia at the total hip and femoral neck, while rs16835198 was associated as a protector for presence of osteopenia only at the femoral neck.

ASSOCIATION BETWEEN APOE-ε4 CARRIER STATUS AND QUALITATIVE NEUROIMAGING CHARACTERISTICS IN OLDER ADULTS WITH MILD COGNITIVE IMPAIRMENT.

BACKGROUND: The pathogenesis of mild cognitive impairment (MCI) is multifactorial and includes the presence of genetic variants such as the ε4 allele of the apolipoprotein E gene (APOE-ε4). Association between the APOE-ε4 carrier status and deleterious structural and functional changes on magnetic resonance imaging (MRI) has been previously described in individuals with Alzheimer's disease. However, the central nervous system changes may possibly develop in earlier stages of cognitive impairment, as reflected in MCI. OBJECTIVE: The objective of the study was to determine the association between APOE-ε4 carrier status and qualitative changes on MRI (medial temporal and parietal atrophy), as well as the detection of white matter hyperintensities (WMH) in older adults with MCI, in the memory clinic of a tertiary care hospital in Mexico City. METHODS: A cross-sectional study of 72 adults aged 60 years or above who underwent an exhaustive clinical, neuroimaging, and neuropsychological evaluation. Multivariate logistic regression models were constructed to determine the association between APOE-ε4 carrier status and qualitative/quantitative changes on MRI. RESULTS: Mean age was 75.2 years (± 7.2) and 64% were female. Twenty-one participants were cognitively normal and 51 had MCI. Almost 56% were APOE-ε4 carriers and were associated with medial-temporal atrophy according to the Scheltens scale (odds ratio [OR]: 20.0, 95% confidence intervals [CI]: 3.03-131.7), parietal atrophy according to the Koedam's score (OR: 6.3; 95% CI 1.03-39.53), and WMH according to the Fazekas scale (OR: 11.7, 95% CI: 1.26-108.2), even after adjusting for age, educational level, and cardiovascular risk factors. CONCLUSION: The APOE-ε4 carrier status was associated with medial temporal and parietal atrophy, as well as WMH. Our findings support the hypothesis suggesting the contribution of this genotype to neurodegeneration and cerebral vascular pathology.

Study of 17 X-STRs in Native American and Mestizo populations of Central America for forensic and population purposes.

In the present work, an extensive analysis of the X-chromosomal pool of Native American and Mestizo groups of Central America (Guatemala, El Salvador, Nicaragua, and Panama) has been carried out. Allele and haplotype frequency databases, as well as other forensic parameters for these populations, are presented. The admixture analysis supports the tri-hybrid composition in terms of ancestry in the Mestizo populations, with a predominant Native American contribution (54-69%), followed by European (19-28%) and African contributions (12-19%). Pairwise FST genetic distances highlight the genetic proximity between the northernmost Central American populations, especially among admixed populations. The unique and complex nature of this area, where populations from different origins intercrossed, as well as the informativity of X-STR data, highpoint the great interest of this genetic study. Furthermore, the X-chromosome databases for Central American populations here provided will be not only useful for forensic and population purposes not only in the target countries but also in the host countries.

Investigating genetic diversity in admixed populations from Ecuador.

OBJECTIVES: According to demographic history, Ecuador has experienced shifts in its Native American populations caused by European colonization and the African slave trade. The continuous admixture events among Europeans, Native Americans, and Africans occurred differently in each region of the country, producing a stratified population. Thus, the aim of this study was to investigate the level of genetic substructure in the Ecuadorian Mestizo population. MATERIALS AND METHODS: A total of 377 male and 209 female samples were genotyped for two sets of X-chromosomal markers (32 X-Indels and 12 X-STRs). Population analyses performed included Hardy-Weinberg equilibrium tests, LD analysis, PCA, pairwise FST s, and AMOVA. RESULTS: Significant levels of LD were observed between markers separated by distances of less than 1 cM, as well as between markers separated by distances varying from 10.891 to 163.53 cM. Among Ecuadorian regions, Amazonia showed the highest average R2 value. DISCUSSION: When X-chromosomal and autosomal differentiation values were compared, a sex-biased admixture between European men and Native American and African women was revealed, as well as between African men and Native American women. Moreover, a distinct Native American ancestry was discernible in the Amazonian population, in addition to sex-biased gene flow between Amazonia and the Andes and Pacific coast regions. Overall, these results underline the importance of integrating X chromosome information to achieve a more comprehensive view of the genetic and demographic histories of South American admixed populations.

Bone mineral density and fractures in postmenopausal women of Maya-Mestizo ethnic origin with different body mass indexes.

BACKGROUND: Obesity protects against bone loss, but it increases the risk of fragility fractures. AIM: To determine if bone mineral density (BMD) and the prevalence of fractures are different in postmenopausal Maya-Mestizo women grouped according to their body mass index (BMI). SUBJECTS AND METHODS: We studied 600 postmenopausal Maya-Mestizo women. A structured questionnaire for risk factors was applied. Body mass index was determined. BMD was assessed at the lumbar spine and total hip by dual-energy X-ray absorptiometry. History of low trauma fracture was determined from medical records. ANOVA was used to compare mean BMD between women with different BMI. To compare the frequency of fractures according to BMI group, we used χ2 test. RESULTS: According to WHO classification of BMI, 16.3% of women had normal BMI, 35.3% were overweight, and 48.4% had obesity. We found that women with obesity had a higher BMD versus women with normal BMI or overweight in all the anatomical sites analysed. The prevalence of history of fractures was 18.2%. We did not find differences between the women of different BMI; the wrist was the most frequent skeletal site of the fracture. CONCLUSION: Obesity in postmenopausal Maya-Mestizo women is not a risk factor for developing fragility fractures.

Different body mass indexes and their relation to prognosis of early-stage breast cancer in postmenopausal Mexican-Mestizo women.

It has been suggested that obesity increases the incidence of metastatic breast tumors, resulting in higher rates of recurrence, and increased mortality; for that reason, the aim of this study was to investigate if different body mass indexes modified the clinicopathologic characteristics of breast cancer; as well as, the recurrence-free survival in postmenopausal Mexican-Mestizo women. Two hundred twenty postmenopausal women with operable breast cancer were included. A structured questionnaire was applied to explore the existence of potential risk factors. Body mass index (BMI) was determined in each case and patients were grouped in accordance to their BMI in: normal weight, overweight, or obesity. Kaplan-Meier survival analysis and log-rank statistic were used to estimate recurrence-free-survival differences. Hormonal receptor(+)/HER2(-) was the most frequent breast cancer in all groups. Overweight women presented a statistically significant increased risk of this molecular subtype, with an odds ratio (OR) = 5.57; 95% confidence interval (CI) = 1.54-24.86; P = .004)). In addition, the triple-negative subtype was more frequent in women with a normal BMI in comparison to women with overweight (P = .016) or women with obesity. The heterogeneity in cancer subtypes regarding BMI was observed.

Association between vitamin D deficiency and common variants of Vitamin D binding protein gene among Mexican Mestizo and indigenous postmenopausal women.

PURPOSE: Vitamin D deficiency (VDD) and polymorphisms in the group-specific component (GC) gene are known to be associated in different populations. However, the effects of such genetic variants may vary across different populations. Thus, the objective of this study was to estimate the association between Vitamin D-Binding Protein (VDBP) haplotypes and VDD in mestizo postmenopausal women and Mexican Amerindian ethnic groups. METHODS: This was a cross-sectional study of 726 postmenopausal Mexican women from the Health Workers Cohort Study (HWCS) and 166 postmenopausal women from the Metabolic Analysis in an Indigenous Sample (MAIS) cohort in Mexico. GC polymorphisms (rs7045 and rs4588) were analyzed by TaqMan probes. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured by Chemiluminescent Microparticle Immuno Assay. RESULTS: The prevalence of VDD serum 25(OH)D < 20 ng/mL was 43.7% in mestizo women and 44.6% in indigenous women. In HWCS, the single nucleotide polymorphisms (SNPs) rs7041 and rs4588 were associated with VDD. In addition, women from the HWCS, carrying the haplotypes GC2/2 and GC1f/2 had higher odds of VDD (OR = 2.83, 95% CI 1.14, 7.02; and OR = 2.30, 95% CI 1.40, 3.78, respectively) compared to women with haplotype 1f/1 s. These associations were not statistically significant in the MAIS cohort. CONCLUSIONS: Our results show genetic association of the analyzed SNPs and related haplotypes, on the GC gene, with VDD in mestizo Mexican postmenopausal women. Moreover, a high prevalence of VDD with high genetic variability within the country was observed. Our results support the need for national policies for preventing VDD.

CORONARY ARTERY CALCIUM IS ASSOCIATED WITH LPA GENE VARIANT RS7765803-C IN MEXICAN MESTIZO POPULATION. THE GEA PROJECT.

BACKGROUND: Lipoprotein(a) [Lp(a)] levels are genetically determined; high levels are a risk factor for coronary disease, although their association with coronary artery calcium (CAC) is controversial. Objective: The objective of the study was to assess the association of LPA gene polymorphisms with CAC in a Mexican Mestizo population. METHODS: We included 1594 subjects 35-70 years old. Six polymorphisms of the LPA gene were analyzed. CAC score was determined by tomography and Lp(a) serum levels by immunonephelometry. The association of LPA polymorphism with CAC and Lp(a) was evaluated by logistic regression. RESULTS: The prevalence of Lp(a) ≥30 mg/dL was 10%, and of CAC >0 was 26.9%. Three polymorphisms were associated with high Lp(a) levels: rs10455872-G (p = 0.013), rs6907156-T (p = 0.021), and rs7765803-C (p = 0.001). Homozygotes (CC) for the rs7765803 variant compared with the G allele (CG + GG) carriers had higher Lp(a) levels (8.9 [3.3-23.9] vs. 4.9 [2.3-11.2] mg/dL; p = 0.015) and higher prevalence of CAC >0 (36.5% vs. 26.3%, p = 0.045) and were associated with CAC > 0 (odds ratio = 1.7, 95% confidence interval: 1.06-2.7; p < 0.026). The other polymorphisms were not associated with CAC. CONCLUSIONS: This is the first study to demonstrate in a Mexican Mestizo population that carriers of the rs7765803-C allele of LPA gene have 2.6 times greater risk for high Lp(a) values and 1.7 times higher risk for coronary artery disease.

WHOLE SEQUENCING OF THE MITOCHONDRIAL GENOME OF BREAST CANCER TISSUE IN MEXICAN-MESTIZO POSTMENOPAUSAL WOMEN WITH DIFFERENT BODY MASS INDEX.

BACKGROUND: Mitochondrial and oxidative stress has been related to obesity and breast cancer being this cancer more frequent and more aggressive in postmenopausal women with obesity. OBJECTIVE: The objective of this study was to investigate whether Mexican-Mestizo postmenopausal women with breast cancer and obesity present different somatic mutations in the mitochondrial DNA (mtDNA) when compared to women with normal body mass index (BMI). SUBJECTS AND METHODS: We included six Mexican-Mestizo postmenopausal women bearing breast cancer and who underwent mastectomy or breast-conserving surgery. BMI was determined in each case. Patients' genomic DNA was isolated from blood leukocytes and tumor tissue samples. Whole mtDNA sequence was determined by MitoChip v2.0 mitochondrial resequencing array, and data were analyzed using the GeneChip Sequence Analysis Software. Tumor mtDNA sequence was compared with matched leukocyte mtDNA sequence. RESULTS: Three women had a normal BMI and three presented obesity. Overall, we found 64 genetic variants: 53.1% were somatic mutations and 46.9% were polymorphisms; 44.1% were in the non-coding region and 55.9% were in genes that encode for mitochondrial proteins. Among the somatic mutations, 67.7% were in patients with normal BMI and 32.3% in patients with obesity. CONCLUSIONS: We did not find a higher frequency of mitochondrial somatic mutations in postmenopausal women with breast cancer and obesity compared to those with normal BMI. However, results could be due to the small number of women studied.

Influence of proinflammatory cytokine gene polymorphisms on the risk of COPD and the levels of plasma protein.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a complex and multifactorial disease involving systemic inflammation. Although certain genetic components have been implicated in the development and progression of this disease, few studies have examined the participation of polymorphisms in proinflammatory genes and the extent to which polymorphisms are related to plasma levels of cytokines involved in the inflammatory process. METHODS: Of the 1125 smokers participating in the study, 438 had COPD, and 687 did not. We determined the genotype of 5 SNPs distributed in the genes: IL6, CXL8, CSF2, CCL1 and IL1B. The plasma protein expression of these genes was also evaluated and categorized according to genotype and the severity of COPD (GOLD grade). RESULTS: An analysis using the codominant model showed an association between rs1818879 in IL6 and susceptibility to COPD (GA OR = 1.1, AA OR = 1.77; p < 0.01), as well as an association between rs25882 in CSF2 and a greater severity of the disease (TC OR = 1.84, CC OR = 3.62; p < 0.01). No association was found between the presence of certain alleles in the SNPs and the plasma levels of the corresponding proteins. CONCLUSIONS: There are genetic polymorphisms related to susceptibility to COPD (rs1818879/A in IL6), as well as to the risk of greater severity of the disease (rs25882/T in CSF2). The presence of the alleles of interest did not significantly affect plasma levels of the codified proteins.

Factors associated with health-related quality of life in Peruvian patients with systemic lupus erythematosus.

Objective In this paper, we aim to define factors associated with health-related quality of life (HRQoL) in Mestizo patients with systemic lupus erythematosus (SLE). Methods We evaluated patients with SLE from Peru's two largest hospitals between October 2012 and July 2015 to ascertain HRQoL. Using a standard protocol, we incorporated demographic characteristics, clinical manifestations and treatment in our analysis. HRQoL was measured with the LupusQoL, disease activity was ascertained with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and damage was appraised with the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) damage index (SDI). The associations between the LupusQoL and these variables were examined using linear regression models. Model selection was based on backward elimination. Results A total of 277 patients fit the inclusion criterion. Of these, 254 (91.7%) were female, the median (interquartile range, IQR) age at diagnosis was 41.5 (33.8-51.8) years, disease duration was 6.5 (2.7-11.3) years. The HRQoL domains most affected were the following: burden to others, fatigue, and intimate relationships. Through multivariate analysis, we determined that older age at diagnosis, higher disease activity, damage, and immunosuppressive drug use were negatively associated with HRQoL. Further, we found that higher socioeconomic status, disease duration, and antimalarial use were positively associated with HRQoL. Conclusion Age at diagnosis, disease activity, damage, and use of immunosuppressive drugs were negatively associated with HRQoL; high socioeconomic status, disease duration, and use of antimalarials were positively associated with HRQoL.

Urinary neutrophil gelatinase-associated lipocalin and monocyte chemoattractant protein 1 as biomarkers for lupus nephritis in Colombian SLE patients.

Background Information regarding urinary biomarkers in Mestizo and Afro-Latin-American patients is very limited. We investigated whether levels of urinary neutrophil gelatinase-associated lipocalin (NGAL), and monocyte chemoattractant protein 1 (MCP-1) are good biomarkers to differentiate patients with lupus nephritis among Latin-American systemic lupus erythematosus (SLE) patients. Methods SLE patients meeting the revised American College of Rheumatology classification criteria for SLE were recruited. Urinary levels of NGAL and MCP-1 were measured using a commercial ELISA kit. Serum anti-C1q antibodies were measured by ELISA. SLE activity was measured with the systemic lupus erythematosus disease activity index (SLEDAI). Mann-Whitney tests were used to compare data and Spearman's rank correlations were used to examine associations between continuous variables. In addition, receiver operating characteristic curves were performed. Results One hundred and twenty SLE patients were recruited (87% women) with a median age of 32.8 ± 12.1 years and median disease duration of 7.3 ± 6.9 years. Afro-Latin-Americans had a significantly higher prevalence of lupus nephritis and higher SLEDAI scores than Mestizos. The three biomarkers were significantly higher in patients with lupus nephritis than in patients without lupus nephritis. In addition, urinary NGAL and MCP-1 were significantly higher in patients with active lupus nephritis than in inactive lupus nephritis. Urinary NGAL levels were significantly higher in Afro-Latin-American patients. A receiver operating characteristic curve for urinary biomarkers for lupus nephritis in all SLE patients showed a good level of sensitivity and specificity. Conclusion In our cohort of SLE patients, we found that urinary NGAL and MCP-1 in addition to anti-C1q antibodies were useful biomarkers for the identification of renal involvement and discrimination of active lupus nephritis among patients with renal disease.

In vitro determination of Mexican Mestizo hair shaft diameter using optical coherence tomography.

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.

Higher prepregnancy body mass index is a risk factor for developing preeclampsia in Maya-Mestizo women: a cohort study.

AIM: Preeclampsia and obesity are two closely related syndromes. The high maternal prepregnancy body mass index (BMI) is a risk factor for present preeclampsia, independently of the ethnic background of the studied population. The aim of this study was to analyse in a prospective cohort study the relation between prepregnancy BMI and development of preeclampsia in Maya-Mestizo women. DESIGN: This is a prospective cohort study of 642 pregnant women that were included in the first trimester of the pregnancy (gestational age ≤12 weeks at the first antenatal visit) and all of them were of Maya-Mestizo ethnic origin from the state of Yucatán, México. We assessed the potential risk factors for preeclampsia and documented the prepregnancy BMI (kg/m2) that was based on measured height and maternal self-report of prepregnancy weight at the initial visit. Besides, in the antenatal visit we documented if the pregnant women developed preeclampsia. RESULTS: Of the 642 pregnant Maya-Mestizo women, 49 developed preeclampsia, with an incidence of 7.6% (44.9% had severe and 55% mild). The prepregnancy BMI was higher in women with developed preeclampsia than in those with normal pregnancies. Women with overweight or obesity in comparison with normal weight presented a RR = 2.82 (95% CI: 1.32-6.03; P = 0.008) and RR= 4.22 (95% CI: 2.07-8.61; P = 0.001), respectively. CONCLUSIONS: Our findings expand the previous studies to show that the higher prepregnancy BMI is a strong, independent risk factor for preeclampsia.

Complete sequence of the ATP6 and ND3 mitochondrial genes in breast cancer tissue of postmenopausal women with different body mass indexes.

Due to the fact that mitochondrial defects and oxidative stress have been related with obesity and breast cancer is more aggressive in women with obesity, we investigated if postmenopausal Mexican-Mestizo women with breast cancer presented somatic mutations in the sequence of the ATP6 and/or ND3 genes. Twenty one postmenopausal Mexican-Mestizo women with breast cancer who underwent mastectomy or breast conserving surgery were studied. Height and weight were used to calculate body mass index. DNA from tumor tissue samples and blood leukocytes was amplified by polymerase chain reaction and sequenced the ATP6 and ND3 mitochondrial genes. Ages ranged from 46 to 82. According to World Health Organization criteria among the 21 women, 7 had a normal BMI, 7 were overweight and 7 had obesity. In regard to the molecular study, after sequencing the coding region of ATP6 and ND3 genes of the DNA obtained from both leukocytes and tumor tissue, we did not find somatic mutations. All of the changes that we found in both genes were polymorphisms: in ATP6, we identified in ten patients 3 non-synonymous nucleotide changes and in ND3 we observed that six patients presented polymorphisms, three of them were synonymous and two non-synonymous. To our knowledge, this constitutes the first report where the complete sequence of the ATP6 and ND3 genes has been analyzed in postmenopausal Mexican-Mestizo women with breast cancer and diverse BMI. Our results differ with those reported in Caucasian and Asian populations, possibly due to ethnic differences.

Multiple Sclerosis in Latin Americans: Genetic Aspects.

Latin Americans (LA) are a heterogeneous, multiethnic group of individuals who inhabit the continental countries in Latin America (LATAM), Caribbean islands and constitute the largest ethnic minority in the USA. Commonly used terminology and ethno racial classifications to define these groups may not be accurate. Risk for multiple sclerosis (MS) among LA is generally low to medium but frequencies are increasing in the American hemisphere. Genome-Wide Association Studies (GWAS) in LA show diverse variants and genetic proportions among Mestizos, the most representative ethnic population, who themselves are the product of centuries of interracial mixing between Native Americans (or Amerindians), White Caucasian Europeans, and Black Africans. Genetic distribution diversity appears to be related to migratory and historical and socio-political factors in LATAM. Epidemiologic studies show an extremely low prevalence of MS among non-mixed Amerindians; this has been attributed to protective ancestral Asian genetics and possibly, environmental factors. Mestizos and biracial LA of African ancestry have more susceptibility to MS apparently due to the historical introduction of the European HLA-DRB1*1501 gene. Contribution from HLA typing, GWAS, and ancestry informative markers (AIMs) has been determinant in the current LA genetic understanding but more regional studies are needed. The relationship between genetics and disease regional distribution is emphasized.

Association of CYP1A1 and CYP1B1 polymorphisms with bone mineral density variations in postmenopausal Mexican-Mestizo women.

Herein, we investigated potential associations between polymorphisms of genes related to estrogen metabolism and bone mineral density (BMD) in postmenopausal women. This was a cross-sectional study, in which two hundred and ninety postmenopausal Mexican-Mestizo women were studied. The BMD of the lumbar spine (LS), total hip (TH), and femoral neck (FN) was measured. The distribution of the genetic polymorphisms, including rs1799814 and rs1048943 at CYP1A1 as well as rs1056836 at CYP1B1, were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), single-stranded conformational polymorphism (SSCP), and DNA sequencing. Deviations from Hardy-Weinberg equilibrium (HWE) were tested, and linkage disequilibrium (LD) was calculated by direct correlation (r2). Moreover, haplotype analysis was performed. All polymorphisms were in HWE. The genotype and allele distributions of the three single nucleotide polymorphisms (SNPs) studied showed no significant differences. However, statistical significance was reached when constructing haplotypes. The CG haplotype in CYP1A1 was associated with variations in LS and FN BMD after adjustment for covariates (p = 0.021 and 0.045, respectively), but the association with TH BMD was not significant. These results suggested that the CG haplotype in CYP1A1 may play an important role in the mechanism of osteoporosis and may be useful as a genetic marker.

Killer cell immunoglobulin-like receptor and human leukocyte antigen gene profiles in a cohort of HIV-infected Mexican Mestizos.

Killer cell immunoglobulin-like receptors (KIRs) represent the most polymorphic genes responsible for natural killer cell function, while human leukocyte antigen (HLA) class I molecules define and restrict cytotoxic T lymphocyte responses. Specific KIR, HLA, or KIR-HLA combinations have been implicated in the outcome of human immunodeficiency virus (HIV) disease. The remarkable polymorphism of KIR and HLA genes warrants descriptive gene frequency studies in different populations, as well as their impact on HIV disease progression in different immunogenetic contexts. We report KIR and HLA class I gene profiles of 511 unrelated HIV-infected Mexican Mestizo individuals from 18 states for whom genetic ancestry proportions were assessed. KIR and HLA gene profiles were compared between individuals from the north and central-south regions of the country and between individuals with higher European (EUR) or Amerindian (AMI) genetic ancestry component. A total of 65 KIR genotypes were observed, 11 harboring novel KIR gene combinations. A total of 164 HLA alleles were observed: 43 HLA-A, 87 HLA-B, and 34 HLA-C. Differences in the distribution of 12 HLA alleles were observed between individuals with higher AMI or EUR ancestry components (p < 0.05, q < 0.2). After correcting for genetic ancestry, only individual HLA alleles were associated with HIV disease progression, including a novel association with A*02:06, an Amerindian HLA allele associated with lower CD4+ T cell counts. No KIR effects were significant. Our results highlight the advantages of considering a detailed genetic stratification within populations when studying genetic profiles that could be implicated in disease-association studies.

Polymorphisms of APLN-APLNR system are associated with essential hypertension in Mexican-Mestizo individuals.

The aim of this study was to evaluate if polymorphisms of APLN and APLNR genes may play a role as susceptibility markers for hypertension in a group of Mexican-Mestizo patients. A case-control study was carried out including normotensive and hypertensive individuals. For these, two polymorphisms of APLN (rs3761581 and rs56204867) and two of APLNR () genes were genotyped by 5' exonuclease TaqMan assay in 400 normotensive individuals and 383 patients. The results showed that, under an additive model adjusted by BMI, HDL, triglycerides, glucose and family history of essential hypertension, the rs7119375 and rs10501367 polymorphisms of APLNR gene were associated significantly with a decreased risk of essential hypertension (P=0.039 and P=0.029, respectively). Besides, the haplotypes analysis of these polymorphisms showed that H1 haplotype was associated with an increased risk of essential hypertension (P=0.026), while the H2 haplotype was associated with a decreased risk (P=0.032). Contrary, the rs3761581 and rs56204867 polymorphisms of APLN gene were not associated with essential hypertension (P=0.1707 and P=0.0769, respectively). The data suggest that APLNR rs7119375 and rs10501367 are associated with a decreased risk of essential hypertension in our Mexican-Mestizo studied group, but further studies are warranted.

Population data of 23 STR loci (PowerPlex® Fusion System) in Mexican Mestizos from the West Region.

We analyzed 238 unrelated Mestizo (admixed) individuals from the West region of Mexico with the PowerPlex® Fusion System (Promega Corp.). Allele frequencies and forensic parameters were estimated for the 23 STRs included in this kit. Hardy-Weinberg equilibrium by locus and non-association between pair of loci were demonstrated by exact tests in this population. The combined PE and PD offered by this HID kit were ≥0.9999999986, representing a substantial improvement with respect to those previously offered by 15 STR systems. Interpopulation comparison by AMOVA tests demonstrated low but significant differences among Mexican Mestizos from West, Center, and Northeast regions (Fst = 0.01558; p = 0.0000), similar to the observed among three main ethnic groups from USA (Fst = 0.02048; p = 0.0000). This finding is consistent with the contrary clines of European and Amerindian ancestries described throughout the Mexican territory for Mestizos, the largest population (~90 %) in this country.