Cuestionario de reacciones vasovagales a la donación de sangre en una institución de salud / Questionnaire of vasovagal reactions to blood donation in a health institution

Resumen: Objetivo: Identificar mediante un cuestionario de signos y síntomas vasovagales a donadores de sangre, con el fin de registrar los antecedentes que aumentan la probabilidad de presentar reacciones vasovagales. Materiales y Métodos: Se aplico un cuestionario a donadores de sangre, durante tres meses, en el banco de sangre en una institución de salud de tercer nivel. Resultados: El 100% de los donadores respondió negativamente a las preguntas del cuestionario, pero el 1.3% de ellos presentaron reacción vasovagal, siendo el mareo, palidez y náusea el signo y síntomas más frecuentemente mostrados. Al comparar dos grupos con y sin reacción vasovagal pareados por sexo, edad e índice de masa corporal, no hubo diferencias entre ellos. Conclusiones: Los donadores en nuestro país son fundamentalmente de reemplazo, por lo que se debe considerar esta circunstancia además de sus motivaciones, para el diseño de encuestas dirigidas a esta población.

Abstract: Objective: Identify, trough a vasovagal signs and symptoms questionnaire, blood donors in order to record the antecedents that increases the probability of presenting vasovagal reactions. Materials and Methods: A questionnaire was applied to blood donors, for three months, in the blood bank in a third-level health institution. Results: 100% of the donors answered negatively to the questions in the questionnaire, but 1.3% of them presented vasovagal reaction, with dizziness, pallor and nausea being the most frequently shown sing and symptoms. When comparing two groups with and without vasovagal reaction matched by sex, age and body mass index, there were no differences between them. Conclusions: Donors in our country are fundamentally replacement donors, so this circumstance plus their motivations should be considered for the design of surveys aimed at this population.

Time-Frequency Analysis of Cardiovascular and Cardiorespiratory Interactions During Orthostatic Stress by Extended Partial Directed Coherence.

In this study, the linear method of extended partial directed coherence (ePDC) was applied to establish the temporal dynamic behavior of cardiovascular and cardiorespiratory interactions during orthostatic stress at a 70° head-up tilt (HUT) test on young age-matched healthy subjects and patients with orthostatic intolerance (OI), both male and female. Twenty 5-min windows were used to analyze the minute-wise progression of interactions from 5 min in a supine position (baseline, BL) until 18 min of the orthostatic phase (OP) without including pre-syncopal phases. Gender differences in controls were present in cardiorespiratory interactions during OP without compromised autonomic regulation. However in patients, analysis by ePDC revealed considerable dynamic alterations within cardiovascular and cardiorespiratory interactions over the temporal course during the HUT test. Considering the young female patients with OI, the information flow from heart rate to systolic blood pressure (mechanical modulation) was already increased before the tilt-up, the information flow from systolic blood pressure to heart rate (neural baroreflex) increased during OP, while the information flow from respiration to heart rate (respiratory sinus arrhythmia) decreased during the complete HUT test. Findings revealed impaired cardiovascular interactions in patients with orthostatic intolerance and confirmed the usefulness of ePDC for causality analysis.

Dynamics of the cardiovascular autonomic regulation during orthostatic challenge is more relaxed in women.

Linear dynamic analysis of cardiovascular and respiratory time series was performed in healthy subjects with respect to gender by shifted short-term segments throughout a head-up tilt (HUT) test. Beat-to-beat intervals (BBI), systolic (SYS) and diastolic (DIA) blood pressure and respiratory interval (RESP) time series were acquired in 14 men and 15 women. In time domain (TD), the descending slope of the auto-correlation function (ACF) (BBI_a31cor) was more pronounced in women than in men (p<0.05) during the HUT test and considerably steeper (p<0.01) at the end of orthostatic phase (OP). The index SYS_meanNN was slightly but significantly lower (p<0.05) in women during the complete test, while higher respiratory frequency and variability (RESP_sdNN) were found in women (p<0.05), during 10-20 min after tilt-up. In frequency domain (FD), during baseline (BL), BBI-normalized low frequency (BBI_LFN) and BBI_LF/HF were slightly but significantly lower (p<0.05), while normalized high frequency (BBI_HFN) was significantly higher in women. These differences were highly significant from the first 5 min after tilt-up (p<0.01) and highly significant (p<0.001) during 10-14 min of OP. Findings revealed that men showed instantaneously a pronounced and sustained increase in sympathetic activity to compensate orthostatism. In women, sympathetic activity was just increased slightly with delayed onset without considerably affecting sympatho-vagal balance.

Cardiovascular and Cerebral Hemodynamics in Asymptomatic Healthy Subjects With/Without Abnormal Head-up Tilt Test Versus Recurrent Fainters.

PURPOSE: The aim of this study was to compare hemodynamic and autonomic responses during head-up tilt test (HUTT) between healthy volunteers and patients with a history of fainting and confirmed vasovagal syncope. We hypothesize that the autonomic and hemodynamic physiologic responses remain intact during orthostatic stress in people without previous fainting and negative HUTT, but deteriorate similarly in patients with recurrent vasovagal syncope and in asymptomatic healthy subjects who develop a vasovagal response during HUTT. METHODS: The study included 57 asymptomatic healthy volunteers (42% women, mean age 23.7 ± 3.6 years) categorized as negative HUTT (n = 41) and positive HUTT (n = 16). They were compared with 14 patients (50% women, mean age 24.2 ± 6.1 years) with previous spontaneous recurrent syncope and inducible vasovagal response during HUTT. Cerebral and cardiovascular hemodynamic variables were assessed noninvasively during the HUTT in each participant. RESULTS: In all patients with recurrent syncope, tilt was positive after a mean delay of 15.6 ± 8.6 minutes and did not differ from the time to syncope observed after 19.6 ± 6.9 minutes in asymptomatic healthy subjects with a positive test. A significant decrease throughout the tilting was observed in the blood pressure, peripheral resistances, cerebral blood flow, and vascular efferent sympathetic regulation in both groups of subjects with a positive test. CONCLUSIONS: This study shows that there are subjects, without a history of syncope, who have a positive HUTT with hemodynamic and autonomic responses alike to patients with confirmed vasovagal syncope, precluding them to be selected as controls in vasovagal syncope studies.

Temporal Analysis of Cardiovascular and Respiratory Complexity by Multiscale Entropy Based on Symbolic Dynamics.

The effect of an orthostatic stress on cardiovascular and respiratory complexity was investigated to detect impaired autonomic regulation in patients with vasovagal syncope (VVS). A total of 16 female patients and 12 age-matched healthy female subjects were enrolled in a passive 70° head-up tilt test. Also, 12 age-matched healthy male subjects were enrolled to study gender differences. Analysis was performed dynamically using various short-term (5 min) windows shifted by 1 min as well as by 20 min of orthostatic phase (OP) to evaluate local and global complexity. Complexity was determined over multiple time scales by the established method of refined composite multiscale entropy (RCMSE) and by a new proposed method of multiscale entropy based on symbolic dynamics (MSE-SD). Concerning heart rate variability (HRV) during OP, both methods revealed the highest complexity for female controls followed by lower complexity in male controls (p < 0.01) and by the lowest complexity in female patients (p < 0.01). For blood pressure variability (BPV), no gender differences in controls were shown by any method. However, MSE-SD demonstrated highly significantly increased BPV complexity in patients during OP (p < 0.01 on 4 time-scales after 7 min, p < 0.001 on 5 time-scales after 11 min) while RCMSE did not reveal considerable differences (p < 0.05 on 2 time scales after 7 min). Respiratory complexity was further increased in patients primary shown by MSE-SD. Findings indicated impaired autonomic regulation in VVS patients characterized by predominantly increased BPV complexity accompanied with decreased HRV complexity. In addition, results suggested extending the concept of complexity loss with disease.

Arg347Cys polymorphism of α1a-adrenergic receptor in vasovagal syncope. Case-control study in a Mexican population.

BACKGROUND: Vasovagal syncope is a common clinical condition, consequential to reduced cerebral blood flow resulting from a failure in cardiovascular homeostasis during orthostasis. Blood pressure regulation is the basis for syncope development. In this regulation, the α1a-adrenergic receptor plays a major role. Some studies have found a positive correlation between the Arg347Cys polymorphism of the α1a-adrenergic receptor to hypertension and heart autonomic control. The goal of this study is to evaluate the possible association between the Arg347Cys α1a-adrenergic receptor polymorphism and vasovagal syncope in a Mexican population. METHODS/MAJOR FINDINGS: A sample of 89 vasovagal syncope patients and 40 healthy controls were studied. Arg347Cys α1a-adrenergic receptor polymorphism was determined by the PCR-RFLP method. We found an increased frequency of genotype ArgArg in vasovagal syncope patients. In a logistic regression model significant associations were found in two genetic models, in codominant model (OR=13.21: CI 95% 3.69-54.99, p<0.001) and in additive model (OR=12.68: CI 95% 3.5-53.07, p<0.001) for ArgArg genotype with CysCys as reference. CONCLUSIONS: Our data suggests an important participation of Arg347Cys polymorphism as susceptibility factor in patients with vasovagal syncope. ArgArg genotype could be a marker for vasovagal syncope susceptibility in the Mexican population.

[Genetic study of the vasovagal syncope associated to the Arg389Gly polymorphism of the beta1 adrenergic receptor]. / Estudio genético del síncope vasovagal asociado al polimorfismo Arg389Gly del receptor adrenérgico beta1.

The purpose of this study was to evaluate the correlation between the vasovagal syncope (VVS) and the beta1 adrenergic receptor polymorphism at the 389 position. Seventy individuals with VVS were selected. DNA was extracted from peripheral blood by salting out and subjected to the amplification-restriction test. Genotype identification was made by polyacrylamide gel electrophoresis. A higher frequency in genotype and allele frequencies were found in individuals with positive tilted table test respect individuals with negative test, as well as a marked preference of the GlyGly phenotype in women. Genotype Arg389Gly was the most frequent between individuals with positive response in passive phase with respect to those in the induced phase. When the genotype was analyzed based on the hemodynamic response (VASIS) a gradient is observed in the frequency of Arg389Gly with the highest major frequency in the cardio-inhibitory response followed by the mixed response, and finally the vasodepressor response. These results suggest that the SVV has a genetic component associated with the Arg389Gly polymorphism of the adrenergic receptor. The Gly allele has a high risk association and it is maintained in the population through heterozygosis.

Estudio genético del síncope vasovagal asociado al polimorfismo Arg389Gly del receptor adrenérgico beta1 / Genetic study of the vasovagal syncope associated to the Arg389Gly polymorphism of the beta1 adrenergic receptor

The purpose of this study was to evaluate the correlation between the vasovagal syncope (VVS) and the beta1 adrenergic receptor polymorphism at the 389 position. Seventy individuals with VVS were selected. DNA was extracted from peripheral blood by salting out and subjected to the amplification-restriction test. Genotype identification was made by polyacrylamide gel electrophoresis. A higher frequency in genotype and allele frequencies were found in individuals with positive tilted table test respect individuals with negative test, as well as a marked preference of the GlyGly phenotype in women. Genotype Arg389Gly was the most frequent between individuals with positive response in passive phase with respect to those in the induced phase. When the genotype was analyzed based on the hemodynamic response (VASIS) a gradient is observed in the frequency of Arg389Gly with the highest major frequency in the cardio-inhibitory response followed by the mixed response, and finally the vasodepressor response. These results suggest that the SVV has a genetic component associated with the Arg389Gly polymorphism of the adrenergic receptor. The Gly allele has a high risk association and it is maintained in the population through heterozygosis.

The Arg389Gly beta1-adrenergic receptor gene polymorphism and susceptibility to faint during head-up tilt test.

AIMS: To investigate the association of the Gly389 allele with positive head-up tilt test (HUT) in a Mexican Mestizo population. METHODS AND RESULTS: HUT results were compared between carriers (one or two copies of the Gly389 allele) and non-carriers (Arg389Arg genotype) of the Gly389 allele of the beta(1)AR gene in 50 patients with unexplained syncope. Thirty-three patients (66%) had a positive HUT. Patients with a positive HUT had a higher Gly389 allele frequency compared with those with a negative test (30.3 vs. 3%; OR 13; pC = 0.012). Moreover, when comparing positive HUT in passive drug-free phase, positive HUT in pharmacological (nitrate) phase, and negative (both phases), a decreasing gradient in the frequencies of the Gly389 allele was found among the three groups: 45.4, 22.7, and 3%, respectively. CONCLUSION: An association of positive tilt table testing to a single nucleotide polymorphism with a Gly to Arg switch at position 389 of the beta(1)AR was found. This polymorphism may contribute to susceptibility to faint during orthostatic challenge.

[KCNQ 1 (KvLQT1) missense mutation causing congenital long QT syndrome (Jervell-Lange-Nielsen) in a Mexican family]. / Detección de una mutación en el gen KCNQ1 (KvLQT1) causante de síndrome de Jervell, Lange-Nielsen en una familia mexicana.

BACKGROUND: Long QT syndromes (LQTS) are inherited cardiac disorders caused by mutations in the genes that encode sodium or potassium transmembrane ion channel proteins. More than 200 mutations, in at least six genes, have been found in these patients. The Jervell and Lange-Nielsen (JLN) syndrome is the recessive form of the disease and is associated with deafness. Few families with JLN syndrome and genetic studies are reported in the literature. METHODS: The KCNQ1 (KvLQT1) gene in a Mexican family with Jervell-Lange-Nielsen long QT syndrome was analyzed using an automated sequence method. RESULTS: A missense mutation was found in the three affected individuals. This mutation is associated with complete loss of channel function. Correlation with the phenotype showed a prolonged QTc interval and deafness in the two siblings homozygous to the mutation. The mother, who was heterozygous for the mutation, also had prolonged QTc interval without deafness. The father and younger brother had normal QTc intervals. The mutation was not found in 50 healthy controls studied. CONCLUSIONS: We describe for the first time a mutation in the KCNQ1 gene in a Mexican family with JLN long QT syndrome. This mutation produces an amino acid change (Gly-Arg) at protein level at the 168 residue. This mutation has been previously reported in Caucasian families with LQTS.

Detección de una mutación en el gen KCNQ1 (KvLQT1) causante de síndrome de Jervell, Lange-Nielsen en una familia mexicana / KCNQ 1 (KvLQT1) missense mutation causing congenital long QT syndrome (Jervell-Lange-Nielsen) in a Mexican family

BACKGROUND: Long QT syndromes (LQTS) are inherited cardiac disorders caused by mutations in the genes that encode sodium or potassium transmembrane ion channel proteins. More than 200 mutations, in at least six genes, have been found in these patients. The Jervell and Lange-Nielsen (JLN) syndrome is the recessive form of the disease and is associated with deafness. Few families with JLN syndrome and genetic studies are reported in the literature. METHODS: The KCNQ1 (KvLQT1) gene in a Mexican family with Jervell-Lange-Nielsen long QT syndrome was analyzed using an automated sequence method. RESULTS: A missense mutation was found in the three affected individuals. This mutation is associated with complete loss of channel function. Correlation with the phenotype showed a prolonged QTc interval and deafness in the two siblings homozygous to the mutation. The mother, who was heterozygous for the mutation, also had prolonged QTc interval without deafness. The father and younger brother had normal QTc intervals. The mutation was not found in 50 healthy controls studied. CONCLUSIONS: We describe for the first time a mutation in the KCNQ1 gene in a Mexican family with JLN long QT syndrome. This mutation produces an amino acid change (Gly-Arg) at protein level at the 168 residue. This mutation has been previously reported in Caucasian families with LQTS.

HLA genes in Mexican Teeneks: HLA genetic relationship with other worldwide populations.

The HLA allele frequency distribution of the Mexican Teenek Indians has been studied and compared with those of other First American Natives and worldwide populations (a total of 15694 chromosomes from 73 different populations were analyzed). This study corroborate the restricted HLA polymorphism in the Amerindian populations and demonstrate how the Amerindians show a relatively homogeneity as opposed to other First Native American groups. Finally, the present data support previous ones that state the lack of complete correlation between language and genetics in micro-environmental studies; Teenek Mayan language does not correspond with a close Mayan (Guatemala) relatedness.

Tumor necrosis factor-alpha promoter polymorphism in Mexican patients with Chagas' disease.

The aim of this study was to investigate whether the promoter's polymorphisms at the TNF alpha (TNF-alpha) gene were associated with the genetic susceptibility to Chagas' disease. We analyzed the TNF-alpha (positions -308, and -238) polymorphisms in a sample of 54 serologically positive chagasic individuals and in 169 healthy controls. The patients were divided according to clinical characteristics as asymptomatics (n = 27), and chronic chagasic cardiopathy (CCC) patients (n = 27). The whole group of patients showed increased frequencies of -308 T2 (A) allele when compared to healthy controls (pC = 0.008, OR = 3.03). When the analysis was carried out separately in asymptomatic and CCC patients, increased frequencies of T2 (A) allele and T1T2 (AG) genotype in the group of patients with CCC were found when compared to asymptomatic individuals (pC = 0.0002 and pC = 0.003, respectively) and healthy controls (pC = 4 x 10(-7), OR = 7.02, and pC = 0.0006, OR = 5.29, respectively). The present study demonstrates that Chagas' disease is associated with TNF-alpha polymorphisms in the Mexican population. The TNF-308 T2 allele could be directly involved in the genetic susceptibility to the chronic phase of the disease.

Tumor necrosis factor-alpha -308 promoter polymorphism contributes independently to HLA alleles in the severity of rheumatoid arthritis in Mexicans.

The aim of this study was to determine the frequency and potential relevance of the promoter polymorphisms of the tumor necrosis factor-alpha (TNF-alpha) in the severity of rheumatoid arthritis (RA) in Mexicans. HLA-DR and polymorphisms at positions -238 and -308 of TNF-alpha gene were determined in 137 Mexican RA patients (44 with severe and 93 with non-severe RA) as well as in 169 healthy controls (99 were typed for HLA-DR). We observed an increased frequency of HLA-DR4 in severe RA compared to healthy controls (pC=0.02, OR=2.33). TNF polymorphism analysis showed a significant increased frequency of TNF -238 GG genotype in the whole group of RA patients when compared to healthy controls (pC=0.007, OR=4.71). When the analyses were carried out separately in severe and non-severe RA patients, the increased frequency of -238 GG genotype only was observed in patients with non-severe forms of the disease. Analysis of -308 polymorphism showed increased frequency of -308 T2 (A) allele in severe RA when compared to non-severe disease (pC=0.011, OR=3.29) and to healthy controls (pC=0.002, OR=3.97). The data demonstrate that -308 T2 (A) allele is associated with susceptibility to develop severe RA in Mexicans. This association could be independent from HLA-DR alleles and might be used as a prognostic marker for severe RA.

Matrix gamma-carboxyglutamic acid protein (MGP) G-7A and T-138C gene polymorphisms in Indian (Mayo and Teenek) and Mestizo populations from Mexico.

Matrix gamma-carboxyglutamic acid protein (MGP) genotypes (G-7A and T-138C) were determined in 266 individuals from three Mexican populations. Mexicans showed increased frequencies of the G-7A G allele and the G7-A GG genotype compared to Europeans. For the T-138C genotype, we found differences among the Mexicans. This study could help to define the significance of MGP polymorphisms as genetic markers in Amerindian populations.

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.

Comparative study of the residues 63 and 67 on the HLA-B molecule in patients with Takayasu's Arteritis.

Takayasu's Arteritis (TA) has been associated with the Major Histocompatibility Complex (MHC) genes; nevertheless, results in several populations have been heterogeneous. Studies both in Mexican and Asian populations suggest that residues at positions 63 (glutamic acid) and 67 (serine) of the HLA-B molecule could be the genetic markers for TA. In the present work, we analyzed the sequence of HLA-B alleles in 26 TA patients and 62 healthy controls. HLA-B subtyping analysis showed that all B52 alleles were B*5201, whereas only one HLA-B39 allele was B*3902. Sequencing of HLA-B alleles showed that 19 out of 26 patients studied (73.0%) presented at least an allele with glutamic acid at position 63 and serine at position 67. This condition was observed in only 21.0% of the healthy controls (pC = 0.00001, OR = 10.23). Out of the seven remaining patients, one presented glutamic acid at position 63 and four showed serine at position 67. Two patients (2/26 = 7.7%) and 24 healthy controls (24/62 = 38.7%) did not show similarity at the mentioned positions (pC = 0.016, OR = 0.13). These data corroborate the participation of positions 63 and 67 in the genetic susceptibility to TA and explain the high heterogeneity of alleles associated with the disease in several populations.

Association study of LMP gene polymorphisms in Mexican patients with spondyloarthritis.

To evaluate the role of LMP (low molecular weight protein) genes as susceptibility markers for spondyloarthritis (SpA), LMP gene polymorphisms were analyzed in 223 Mexican patients with SpA (81 undifferentiated SpA [U-SpA], 117 with ankylosing spondylitis [AS], 25 with reactive arthritis) and in 139 ethnically matched healthy individuals. LMP genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. The LMP2 and LMP7 allele frequencies were similar in patients and healthy controls. Genotype analysis revealed an increased frequency of LMP2 R/R genotype in the whole group of SpA (pC = 0.003, OR = 2.06, 95%CI = 1.3-3.25) and in the clinical subgroups of AS (pC = 0.039, OR = 1.88, 95%CI = 1.1-3.22) and U-SpA (pC = 0.003, OR = 2.56, 95%CI = 1.37-4.8) compared with healthy controls. Analysis in the LMP7 did not reveal significant differences in patients and healthy controls. The HLA-B27-negative AS subgroup also showed an increased frequency of LMP2 R/R genotype (pC = 0.027, OR = 4.81, 95%CI = 1.21-22.13). The LMP2-R/R AS patients were younger than LMP2-H/R and H/H patients at onset of the disease (16.0 +/- 6.8 years for R/R, 22.0 +/- 11.2 years for H/R and 28.6 +/- 10.9 years for H/H) (p < 0.05). The data suggest that, besides HLA-B27, LMP2 genotypes are also involved in the genetic susceptibility to develop AS in Mexicans. Furthermore, the age at onset of this disease might also be influenced by genotypes of this gene.

MHC class II alleles in Mexican patients with rheumatic heart disease.

BACKGROUND: Rheumatic heart disease (RHD) is an autoimmune sequel of group A streptococcal infection that has been associated with the presence of some major histocompatibility complex (MHC) genes. Thus, the aim of the present study was to investigate the role of class II alleles in the genetic susceptibility to RHD in Mexican patients and establish the relationship of these alleles with the pattern of valve damage. METHODS: HLA-DR, -DQA1 and -DQB1 allele frequencies were determined by PCR-SSO reverse dot blot and PCR-SSP in 98 Mexican Mestizo patients with RHD and 99 healthy controls. Patients were divided into mitral valve damage (n=46), multivalvular lesion (n=49) and aortic damage (n=3). RESULTS: RHD patients presented an HLA-DR16 increased frequency (pC=0.009, OR=3.9) and a decreased HLA-DR11 frequency (pC=0.018) when compared to healthy controls. HLA-DR16 subtyping showed that DRB1*1602 was the DR16 allele increased in patients (pC=0.007, OR=5.3). Haplotype analysis showed increased frequency of DR16-DQA1*0501-DQB1*0301 in RHD patients when compared to healthy controls (pC=0.011). HLA-DR16 frequency remained significantly increased on patients with multivalvular lesion (pC=0.004, OR=4.8). CONCLUSIONS: Our data suggest an important participation of Amerindian autochthonous HLA-DR16 (DRB1*1602) allele and DR16-DQA1*0501-DQB1*0301 haplotype as markers for RHD genetic susceptibility in the Mexican Mestizo population. HLA-DR16 allele could also play an important role in determining the pattern of valve damage on these patients.