Effect of metabolic control on recurrent major adverse cardiovascular events and cardiovascular mortality in patients with premature coronary artery disease: Results of the Genetics of Atherosclerotic Disease study.

BACKGROUND AND AIMS: Coronary artery disease (CAD) is the leading cause of death around the world, and its rate of presentation is increasing at young ages. Despite the evidence that secondary prevention in CAD reduces the risk of recurrent major adverse cardiovascular events (MACE), no studies have analyzed the composite control of blood pressure, lipids, and glucose control in premature CAD. METHODS AND RESULTS: This was a real-world prospective cohort study of patients with premature CAD. The composite control in blood pressure <140/80 mmHg, LDL-C <70 mg/dL, non-HDL-C <100 mg/dL, and Hemoglobin A1c <8% was considered as metabolic control. The primary endpoint was the occurrence of non-fatal and fatal MACE. The data included 1042 patients with premature CAD. The mean age of the patients was 54.1 ± 8.1 years, 18.5% were women, and had a median follow-up of 59.1 ± 11.8 months. Of them, 7% had non-fatal MACE, and 4% had a fatal MACE. Overall, 21.3% achieved metabolic control, and 3.0% did not achieve any target. Cox regression analysis showed that percutaneous coronary intervention (Hazzard ratio = 1.883 [95% CI, 1.131-3.136]), C-reactive protein (1.046 [1.020-1.073]), blood pressure >140/90 mmHg (2.686 [1.506-4.791]), fibrates (2.032 [1.160-3.562]), calcium channel blockers (2.082 [1.158-3.744]) had greater risk to present a recurrent non-fatal MACE; whereas familial history of premature CAD (2.419 [1.240-4.721]), heart failure (2.139 [1.032-4.433]), LDL-C >70 mg/dL (4.594 [1.401-15.069]), and diuretics (3.328 [1.677-6.605]) were associated with cardiovascular mortality. CONCLUSIONS: The composite goal achievement in lipids, blood pressure and glucose, reduced the risk for recurrent MACE in 80%.

rs3918242 MMP9 gene polymorphism is associated with myocardial infarction in Mexican patients.

Several studies have demonstrated that matrix metalloproteinases (MMPs) play a major role in atherosclerotic plaque disruption and lead to myocardial infarction (MI). We investigated the association between the MMP1 -1607 1G/2G (rs1799750), MMP3 -1612 5A/6A (rs3025058), and MMP9 -1562 C/T (rs3918242) polymorphisms and the risk of developing MI in a Mexican mestizo cohort. The genotype analysis was performed using the restriction fragment length polymorphism-polymerase chain reaction technique in a group of 236 patients with a history of MI and 285 healthy controls. Similar distributions of rs1799750 and rs3025058 were observed in both groups; however, the MMP9 rs3918242 T allele and the CT genotype were associated with the risk of developing MI (OR = 2.32, pC = 0.02 and OR = 2.40, pC = 0.02, respectively). Multiple logistic analysis was performed between MI patients and controls to estimate the risk, and after adjusting for identified risk factors, the CT + TT genotypes of MMP9 rs3918242 were found to be significantly associated with increased risk of developing MI than those with the CC genotype (OR = 2.88, P < 0.01). In summary, our results reveal that the rs3918242 polymorphism of the MMP9 gene plays a major role in the risk of developing MI.

Genetic polymorphisms of interleukin-22 in patients with ulcerative colitis. / Polimorfismos genéticos de interleucina-22 en pacientes con colitis ulcerosa.

BACKGROUND: Ulcerative colitis (UC) is a multifactorial and polygenic disease. Interleukin-22 (IL-22) is an immunomodulatory cytokine that belongs to the IL-10 family. Currently, some IL-22 polymorphisms have been associated with inflammatory processes such as rheumatoid arthritis and psoriasis vulgaris, but there are no studies on UC. AIM: The aim of this work was to study the frequency of polymorphisms of IL-22 in Mexican patients with UC. METHODS: We studied a total of 199 Mexican patients with confirmed UC and 697 healthy controls. All individuals were born in Mexico, at least three family generations earlier. A blood sample was obtained from the UC patients and healthy controls in order to perform DNA extraction and then to determine the frequency of IL-22 polymorphisms (rs2227485, rs2272478, rs2227491). RESULTS: No statistical significance was found in the gene and genotype frequencies of three SNPs of IL-22 (rs2227485, rs2272478, rs2227491) between the UC patients and healthy controls. No association was found between those IL-22 SNPs and clinical features of UC. CONCLUSIONS: There was no association between IL-22 SNPs (rs2227485, rs2272478, rs2227491) and the development of UC in a Mexican population.

MHC2TA and FCRL3 genes are not associated with rheumatoid arthritis in Mexican patients.

Rheumatoid arthritis (RA) is a multifactorial disease. A combination of genetic and environmental risk factors contributes to its etiology. Several genes have been reported to be associated with susceptibility to the development of RA. The MHC2TA and FCRL3 genes have been associated previously with RA in Swedish and Japanese populations, respectively. In two recent reports, we show an association between FCRL3 and juvenile rheumatoid arthritis (JRA), and MHC2TA and acute coronary syndrome (ACS) in Mexican population. We assessed the association between three single nucleotide polymorphisms (SNPs) of the MHC2TA (-168G/A; rs3087456, and +16G/C; rs4774) and FCRL3 (-169T/C; rs7528684) genes and rheumatoid arthritis in Mexican population through a genotyping method using allelic discrimination assays with TaqMan probes. Our case-control study included 249 patients with RA and 314 controls. We found no evidence of an association between the MHC2TA -168G/A and +1614G/C or FCRL3 -169T/C polymorphisms and RA in this Mexican population. In this cohort of Mexican patients with RA, we observed no association between the MHC2TA or FCRL3 genes and this autoimmune disease.

Overweight and obesity as markers for the evaluation of disease risk in older adults.

OBJECTIVES: To explore disease risk through the measurement of BMI scores and waist circumferences in older Mexican adults with favorable health statuses and to determine how this risk is associated with sociodemographic characteristics. METHODS: Using data from the National Health and Nutrition Survey of 2006, we created a cross-sectional design and selected 878 participants (60 years or older) who had favorable health statuses. The demographic data, health status, body mass index (BMI), waist circumference (WC), and an estimation of disease risk (arterial hypertension, diabetes type 2, and metabolic syndrome) were obtained through the survey. RESULTS: The prevalence of overweight, obesity, and abdominal obesity were 42.1%, 29.7%, and 80.9%, respectively. Disease risks, which were classified as least, increased, high, or very high, were 14.7%, 17.5%, 38.7%, and 29.1%, respectively. We observed that younger age has a higher risk for disease and that this decreases as age increases until it becomes minimal. After controlling for some risk factors such as tobacco, alcohol, and physical activity, we observed that being female, younger, and married are all factors significantly associated with a high and very high risk for disease. On the other hand, being indigenous, having a low education level, living in a rural setting are all protective factors with a minimum disease risk. CONCLUSIONS: The prevalence rates of overweight, obesity, and abdominal obesity are high among older Mexican adults. We observed that as age increases, disease risk decreases, which also occurs with some lifestyle factors such as living in a rural setting, being indigenous, having a low education level, and being married.

Genetic variants associated with severe pneumonia in A/H1N1 influenza infection.

The A/H1N1 influenza strain isolated in Mexico in 2009 caused severe pulmonary illness in a small number of exposed individuals. Our objective was to determine the influence of genetic factors on their susceptibility. We carried out a case-control association study genotyping 91 patients with confirmed severe pneumonia from A/H1N1 infection and 98 exposed but asymptomatic household contacts, using the HumanCVD BeadChip (Illumina, San Diego, CA, USA). Four risk single-nucleotide polymorphisms were significantly (p<0.0001) associated with severe pneumonia: rs1801274 (Fc fragment of immunoglobulin G, low-affinity IIA, receptor (FCGR2A) gene, chromosome 1; OR 2.68, 95% CI 1.69-4.25); rs9856661 (gene unknown, chromosome 3; OR 2.62, 95% CI 1.64-4.18); rs8070740 (RPA interacting protein (RPAIN) gene, chromosome 17; OR 2.67, 95% CI 1.63-4.39); and rs3786054 (complement component 1, q subcomponent binding protein (C1QBP) gene, chromosome 17; OR 3.13, 95% CI 1.89-5.17). All SNP associations remained significant after adjustment for sex and comorbidities. The SNPs on chromosome 17 were in linkage disequilibrium. These findings revealed that gene polymorphisms located in chromosomes 1 and 17 might influence susceptibility to development of severe pneumonia in A/H1N1 infection. Two of these SNPs are mapped within genes (FCGR2A, C1QBP) involved in the handling of immune complexes and complement activation, respectively, suggesting that these genes may confer risk due to increased activation of host immunity.

Cost-effective analysis of genotyping using oral cells in the geriatric population.

We evaluated the cost-effectiveness of using buccal swab brushes in comparison with blood samples for obtaining DNA for large epidemiological studies of the elderly population. The data reported here are from the third phase of the Integral Study of Depression among the Elderly in Mexico City's Mexican Institute of Social Security, conducted in 2007. The total cost of the two procedures was determined. The measurement of effectiveness was the quality and quantity of DNA measured in ng/µL and the use of this DNA for the determination of apolipoprotein E (APO E) polymorphism by PCR. Similar rates of amplification were obtained with the two techniques. The cost of the buccal swab brushes, including sample collection and DNA extraction, was US$16.63, compared to the cost per blood sample of US$23.35. Using the buccal swab, the savings was US$6.72 per patient (P < 0.05). The effectiveness was similar. Quantity and quality of DNA obtained were similar for the oral and blood procedures, demonstrating that the swab brush technique offers a feasible alternative for large-scale epidemiological studies.

Human leukocyte antigen typing in tuberculous rheumatism: Poncet's disease.

SETTING: Tuberculous rheumatism (Poncet's disease) is a reactive polyarthropathy associated with extra-pulmonary and pulmonary tuberculosis (TB) without evidence of mycobacterial infection of the involved joints. As all patients with TB do not present with this peculiar clinical feature, a genetic susceptibility is suspected. OBJECTIVE: To determine the major histocompatibility complex (MHC) class I and II alleles in Mexican mestizo patients with Poncet's disease. DESIGN: In this case-control study of 16 Mexican mestizo patients diagnosed with Poncet's disease and 99 ethnically matched healthy controls, high resolution human leukocyte antigen (HLA) typing was performed for HLA-A, B, DR and DQ by polymerase chain reaction. HLA-DRB1 and HLA-DQB1 subtypes were performed by sequence-specific oligonucleotide probe hybridization. RESULTS: A significantly increased frequency of HLA-B27 (corrected P = 0.01) and DQB1*0301 (corrected P = 0.0009) alleles and decreased frequency of HLA-DQB1*0302 (corrected P = 0.00001) were identified in patients compared to healthy controls. CONCLUSION: These data suggest that genes located within the MHC may play a role in the susceptibility to Poncet's disease in patients diagnosed with TB.

Association of HLA DRB1 alleles with juvenile idiopathic arthritis in Mexicans.

OBJECTIVE: The aim of the study was to investigate association between HLA class II alleles and juvenile idiopathic arthritis (JIA) in Mexican patients. PATIENTS AND METHODS: We typed 120 patients with JIA and 99 healthy controls for HLA class II alleles were performed by PCR-SSO. Differences between the whole group of JIA and its subtypes and controls were calculated by using the Xi2; p-values were corrected (pc) with Bonferroni's test. RESULTS: The alleles HLA-DRB1*01 (pc= 0.00083) and HLA-DRB1*04 (pc=0.0049) were strongly associated with systemic JIA, while HLA-DRB1*11 and HLA-DRB1*14 were found to have decreased frequencies in the patients with systemic JIA compared to the controls. Two alleles were found to have increased frequencies with JIA oligoarthritis subgroup, HLA-DRB1*11 (p=0.01, pc=NS) and HLA-DRB1*13 (p=0.01, pc=NS). The HLA-DRB1*04 was found increased frequencies with susceptibility for RF negative and RF positive polyarthritis JIA subgroups (p correction resulted in loss of significance). In contrast two alleles HLA-DRB1*07 and HLA-DRB1*14 were found decreased frequencies only patients RF positive polyarthritis JIA subgroup compared to the controls (pc=NS). CONCLUSION: The profile of HLA-DRB1 alleles associations in Mexican with JIA were somewhat distinct from association typically found in Caucasians.

A/G Gln20Arg (exon 1) and G/A Val156Met (exon 5) polymorphisms of the human orosomucoid 1 gene in Mexico.

The human orosomucoid 1 gene (ORM1) codes an alpha-1-acid glycoprotein that has been classified as an acute-phase reactive protein, and a major drug-binding serum component, as well as an immunomodulatory protein with genetic polymorphisms. Evaluation of ORM variation through isoelectric focusing and immunobloting has revealed a world-wide distribution of the ORM1 F and ORM1 S alleles. We evaluated and examined the genetic characteristics of two Mexican populations that have different anthropological and cultural antecedents, examining two ORM1 genotypes (exon 1 - A/G (Gln20Arg) and exon 5 G/A (Val156Met)) in 145 individuals, using nested polymerase chain reaction, sequencing, and restricted fragment length polymorphism. Mexican Mestizos had higher frequencies of the exon 1 A allele (P = 0.020) and AA genotype (P = 0.018) and lower frequency of the G allele (P = 0.020) when compared to Teenek Amerindians. When we examined exon 5 G/A (Val156Met) polymorphisms, we found significantly higher frequencies of the G allele (P = 0.0007) and the GG genotype (P = 0.0003) in the Mexican Mestizo population. The Teenek population had a significantly higher frequency of the A allele than has been reported for Chinese and African (P < 0.05) populations, and the G/A genotype was more frequently found in this Mexican population than in Chinese, African and European populations (P < 0.05).

A/G Gln20Arg (exon 1) and G/A Val156Met (exon 5) polymorphisms of the human orosomucoid 1 gene in Mexico

The human orosomucoid 1 gene (ORM1) codes an alpha-1-acid glycoprotein that has been classified as an acute-phase reactive protein, and a major drug-binding serum component, as well as an immunomodulatory protein with genetic polymorphisms. Evaluation of ORM variation through isoelectric focusing and immunobloting has revealed a world-wide distribution of the ORM1 F and ORM1 S alleles. We evaluated and examined the genetic characteristicsof two Mexican populations that have different anthropological and cultural antecedents, examining two ORM1 genotypes (exon 1 - A/G (Gln20Arg) and exon 5 G/A (Val156Met)) in 145 individuals, using nested polymerase chain reaction, sequencing, and restrited fragment length polymorphism. Mexican Mestizos had higher frequencies of the exon 1 A allele (P = 0.020) and AA genotype(P = 0.018) and lower frequency of the G allele (P = 0.020) when compared to Teenek Amerindians. When we examined exon 5 G/A (Val156Met) polymorphisms, we found significantly higher frequencies of the G allele (P = 0.0007) and the GG genotype (P = 0.0003) in the Mexican Mestizo population. The Teenek population had a significantly higher frequency of the A allele than has been reported for Chinese and African (P < 0.05) populations, and the G/A genotype was more frequently found in this Mexican population than in Chinese, African and European populations (P < 0.05).

Prospective meta-analysis of interleukin 1 gene complex polymorphisms confirms associations with ankylosing spondylitis.

OBJECTIVES: The aim of the current study was to determine the contribution of interleukin (IL)1 gene cluster polymorphisms previously implicated in susceptibility for ankylosing spondylitis (AS) to AS susceptibility in different populations worldwide. METHODS: Nine polymorphisms in the IL1 gene cluster members IL1A (rs2856836, rs17561 and rs1894399), IL1B (rs16944), IL1F10 (rs3811058) and IL1RN (rs419598, the IL1RA VNTR, rs315952 and rs315951) were genotyped in 2675 AS cases and 2592 healthy controls recruited in 12 different centres in 10 countries. Association of variants with AS was tested by Mantel-Haenszel random effects analysis. RESULTS: Strong association was observed with three single nucleotide polymorphisms (SNPs) in the IL1A gene (rs2856836, rs17561, rs1894399, p = 0.0036, 0.000019 and 0.0003, respectively). There was no evidence of significant heterogeneity of effects between centres, and no evidence of non-combinability of findings. The population attributable risk fraction of these variants in Caucasians is estimated at 4-6%. CONCLUSIONS: This study confirms that IL1A is associated with susceptibility to AS. Association of the other IL1 gene complex members could not be excluded in specific populations. Prospective meta-analysis is a useful tool in confirmation studies of genes associated with complex genetic disorders such as AS, providing sufficiently large sample sizes to produce robust findings often not achieved in smaller individual cohorts.

HLA-DRB1*0101 is associated with the genetic susceptibility to develop lichen planus in the Mexican Mestizo population.

The etiology of lichen planus (LP) is still unknown and previous studies have found an association between LP and HLA-DR1, DR2, DR3, DR9 and DR10 in different populations. The aim of this study was to analyze the distribution of the HLA-DRB1 alleles in Mexican Mestizo patients with LP. The aim of this study was to determine the gene frequency of HLA-DR locus in Mexican Mestizo patients with LP. We studied 20 patients with LP and 99 healthy Mexican Mestizo controls. HLA-DRB1 was performed by PCR-SSO reverse dot blot hybridization. High resolution HLA typing was performed by PCR-SSP. The HLA-DRB1*0101 allele was associated significantly in LP patients compared with healthy controls (pC = 0.0007, OR = 5.46, 95% CI = 1.86-16.06). HLA-DRB1*0101 is a marker for the development of LP in Mexican Mestizo population, yet another gene or HLA marker within MHC region may be the causatively associated gene.

HLA-E polymorphism in Amerindians from Mexico (Mazatecans), Colombia (Wayu) and Chile (Mapuches): evolution of MHC-E gene.

Human leukocyte antigen (HLA)-E is a nonclassical class I (Ib) gene with a restricted polymorphism. Only eight DNA alleles and three proteins of this gene have been described and their frequencies analyzed in Caucasian, Oriental, Asian Indian, and Negroid populations. In the present study, HLA-E polymorphism has been analyzed in six Amerindian and Mestizo populations from North and South America and compared with previously described populations. HLA-E*0101 is the most frequent allele found in all populations except in Afrocolombian and Wayu Amerindians, in which blood group analyses show a high admixture with Caucasian and African populations. Mazatecan and Mapuche (two Amerindian groups from North and South America, respectively) presented similar HLA-E frequencies, whereas Wayu Indians are more similar to the Afrocolombian population. The Mexican and Colombian Mestizo show similar allele frequencies to Amerindians with high frequencies of HLA-E*0101 and HLA-E*010302 alleles. Also, frequencies in Negroids and Asian Indians present a similar distribution of HLA-E alleles. These data are in agreement with worldwide restricted polymorphism of HLA-E because no new allele was detected in the six populations studied. The allelic frequencies show differences among Caucasian, Oriental, Mestizo and Indian populations. Ape major histocompatibility complex-E allelism is also very restricted: common chimpanzee (one allele); bonobo (two alleles); gorilla (two alleles); orangutan (one allele); rhesus monkey (eight alleles); cynomolgus monkey (two alleles); and green monkey (two alleles).

Association of HLA-DRB1*16 with chronic discoid lupus erythematosus in Mexican mestizo patients.

BACKGROUND: Chronic discoid lupus erythematosus (CDLE) is present in 15-30% of patients with systemic lupus erythematosus (SLE). Approximately 5% of CDLE cases can evolve to SLE at some stage of the disease. AIM: The aim of this study was to determine gene frequencies of HLA-DRB1 alleles in Mexican mestizo patients with CDLE, irrespective of the presence of systemic disease. METHODS: The study comprised 28 Mexican mestizo patients with CDLE who were attending the Passover Dermatology Centre, in Mexico City. HLA-DRB1 and DQ allele typing was performed by sequence-specific oligotyping after DNA amplification using PCR. The study also included 99 ethnically matched healthy individuals as controls. RESULTS: In the patient group, a significantly increased gene frequency was found for the HLA-DR4 (P = 0.016, OR = 2.24, 95% CI 1.14-4.38) and HLA-DR16 alleles (P = 0.005, OR = 5.51, 95% CI 1.49-21.08). CONCLUSION: HLA-DRB1 alleles seem to be involved in the genetic susceptibility to CDLE in the Mexican mestizo population.

HLA Genes in Mayos Population from Northeast Mexico.

HLA class I and class II alleles have been studied in 60 unrelated people belonging to Mayos ethnic group, which lives in the Mexican Pacific Sinaloa State. Mayos HLA profile was compared to other Amerindians and worldwide populations' profile. A total of 14,896 chromosomes were used for comparisons. Genetic distances between populations, Neigbour-Joining dendrograms and correspondence analyses were performed to determine the genetic relationship among population. The new specific Mayo HLA haplotypes found are: HLA-A*02-B*35-DRB1*1406-DQB1*0301; HLA-A*02-B*48-DRB1*0404-DQB1*0302; HLA-A*24-B*51-DRB1*0407-DQB1*0302 and HLA-A*02-B*08-DRB1*0407-DQB1*0302. However, the typical Meso American HLADRB1*0407 represents a 40% of all DRB1 alleles. While common HLA characteristics are found in Amerindian distant ethnic groups, still new group specific HLA haplotypes are being found, suggesting that a common founder effect (i.e. high DRB1*0407) is noticed. Moreover, new HLA haplotypes are almost certainly appearing along time probably due to specific pathogen (?) selection for diversity. Mayo language is close to the Tarahumara one (another geographically close group); notwithstanding both groups are not genetically close according to our results, showing again the different evolution of genes and languages, which do not correlate. Finally, Sinaloa is one of the Mexican States in which more European genes are found. However, the results presented in this paper, where no European HLA genes are seen in Mayos, should have a bearing in establishing transplant programs and in HLA and disease studies.

Low grade radiographic sacroiliitis as prognostic factor in patients with undifferentiated spondyloarthritis fulfilling diagnostic criteria for ankylosing spondylitis throughout follow up.

OBJECTIVE: To determine the rate and factors associated with ankylosing spondylitis in a cohort of patients with undifferentiated spondyloarthritides (SpA). METHODS: 62 consecutive patients with undifferentiated SpA seen between 1998 and 1999 underwent clinical and imaging evaluations throughout follow up. The main outcome measure was a diagnosis of ankylosing spondylitis. RESULTS: 50 patients with peripheral arthritis (n = 35) and inflammatory back pain (n = 24) (26 male; mean (SD) age at onset, 20.4 (8.8) years; disease duration 5.4 (5.7) years) were followed up for 3-5 years. At baseline, >90% of patients had axial and peripheral disease, while 38% had radiographic sacroiliitis below the cut off level for a diagnosis of ankylosing spondylitis (BASDAI 3.9, BASFI 2.9). At the most recent evaluation, 21 patients (42%) had ankylosing spondylitis. Two factors were associated with a diagnosis of ankylosing spondylitis in multivariate analysis: radiographic sacroiliitis grade <2 bilateral, or grade <3 unilateral (odds ratio (OR) = 11.18 (95% confidence interval, 2.59 to 48.16), p = 0.001), particularly grade 1 bilateral (OR = 12.58 (1.33 to 119.09), p = 0.027), and previous uveitis (OR = 19.25 (1.72 to 214.39), p = 0.001). Acute phase reactant levels, juvenile onset, and HLA-B27 showed a trend to linkage with ankylosing spondylitis (NS). CONCLUSIONS: Low grade radiographic sacroiliitis is a prognostic factor for ankylosing spondylitis in patients originally classified as having undifferentiated SpA. Low grade radiographic sacroiliitis should be regarded as indicative of early ankylosing spondylitis in patients with undifferentiated SpA.

HLA antigens and juvenile onset spondyloarthritides: negative association with non-B27 alleles.

OBJECTIVE: To describe the association between HLA-B and HLA-DR genes and juvenile onset spondyloarthritides (SpA) in Mexicans. METHODS: The study included 66 consecutive patients with SpA (45 with ankylosing spondylitis (AS) and 21 with undifferentiated SpA) and 99 non-related healthy controls. The HLA-A, -B and DR alleles were detected by the polymerase chain reaction with the sequence-specific primers technique. Statistical methods included the Mantel-Haenzel chi2 test, Fisher's exact test, and Woolf method for odds ratio (OR). RESULTS: The frequency of HLA-B27 was significantly increased in the whole group (pC < 10(-3), OR = 53.0, aetiological fraction = 51%), particularly in AS (pC < 10(-3), OR = 67.42, aetiological fraction 57%). In contrast, the frequencies of HLA-B44, and HLA-B14 were significantly decreased. Also, a weak negative association HLA-DR5 (p < 0.05) was found. CONCLUSION: Apart from an expected significant association between HLA-B27 and juvenile-onset SpA, particularly AS, we found negative associations with HLA-B44, B14, and DR5. There was also a trend for HLA-B15 and DR1 associations with SpA.

HLA-DRB1 alleles encoding the "shared epitope" are associated with susceptibility to developing rheumatoid arthritis whereas HLA-DRB1 alleles encoding an aspartic acid at position 70 of the beta-chain are protective in Mexican Mestizos.

The risk to develop rheumatoid arthritis (RA) has been associated with the presence of HLA-DRB1 alleles encoding the "shared epitope" (SE). Additionally, HLA-DRB1 alleles encoding an aspartic acid at position 70 (D70+ ) have been associated with protection against the development of RA. In this study we tested the association between either SE or D70+ and rheumatoid arthritis in Mexican Mestizos. We included 84 unrelated Mexican Mestizos patients with RA and 99 unrelated healthy controls. The HLA-typing was performed by PCR-SSO and PCR-SSP. We used the chi-squared test to detect differences in proportions of individuals carrying at least one SE or D70+ between patients and controls. We found that the proportion of individuals carrying at least one HLA-DRB1 allele encoding the SE was significantly increased in RA cases as compared to controls (p(c) = 0.0004, OR = 4.1, 95% CI = 2.2-7.7). The most frequently occurring allele was HLA-DRB1*0404 (0.161 vs 0.045). Moreover, we observed a significantly increased proportion of HLA-DRB1 SE+ cases with RF titers above the median (p = 0.005). Conversely, the proportion of individuals carrying at least one HLA-DRB1 allele encoding the D70+ was significantly decreased (p(c) = 0.004, OR = 0.4, 95% CI 0.2-0.7) among RA patients compared with controls. In conclusion, the SE is associated with RA in Mexican Mestizos as well as with the highest titers of RF.