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      Genetic polymorphism of HLA-DRB1 alleles in Mexican mestizo patients with abdominal aortic aneurysms

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          Abstract

          Background

          Multiple factors are implicated in the etiology and pathogenesis of Abdominal Aortic Aneurysms (AAA). Available literature of genetic studies has previously suggested the possible roles of autoimmunity, genetic predisposition and ethnic susceptibility. Due to the association with autoimmune diseases and proven application in population genetics, we aimed to investigate alleles of the Class II Human Leukocyte Antigens (HLA-DRB1) in the Mexican Mestizo population with aortic aneurysms and determine possible associations with susceptibility.

          Methods

          We performed a case Control Study; the HLA molecular typing was completed for DRB1 loci by LabType Sequence-Specific Oligonucleotide (SSO) SSO-OneLambda kit (Applied Biosystems; Thermo Fisher Scientific. Inc.) in the studied individuals. Allele frequencies (af) were determined, associations were assessed by chi square or fisher exact tests at significance level (< 0.05), and Odds Ratios (OR) were calculated using the STATA software version 14.

          Results

          The genetic polymorphism of HLA-DRB1 of fifty one patients (70% males with a mean age of 71 years) with atherosclerotic or also known as degenerative AAA were compared with 99 unrelated patients (60% males, mean age 65 years) without the disease [Control group (CG)] from the same ethnic group. We examined a total of 102 Class II HLA-DRB1 alleles of AAA patients and 198 from CG. When comparing af, we observed the HLA-DRB1*01 af of 0.139 in the AAA compared to 0.05 in the CG [ p = 0.015, OR 3, 95% confidence interval (CI) 1.29–7.08], the HLA-DRB1*16 af were 0.109 in the AAA and 0.025 in CG ( p = 0.006, OR 4.7, 95% CI 1.59–13.98).

          Conclusions

          Our study confirmed increased frequencies of the alleles HLA-DRB1*01 and HLA-DRB1*16 and their association to the development of AAA in Mexican Mestizo patients. The utility of genetic testing may assist in identifying individuals at genetic risk for the development of this disease in different ethnic groups, who might benefit from earlier ultrasound screening and closer imaging surveillance.

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          Most cited references24

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          Analysis of risk factors for abdominal aortic aneurysm in a cohort of more than 3 million individuals.

          Abdominal aortic aneurysm (AAA) disease is an insidious condition with an 85% chance of death after rupture. Ultrasound screening can reduce mortality, but its use is advocated only for a limited subset of the population at risk. We used data from a retrospective cohort of 3.1 million patients who completed a medical and lifestyle questionnaire and were evaluated by ultrasound imaging for the presence of AAA by Life Line Screening in 2003 to 2008. Risk factors associated with AAA were identified using multivariable logistic regression analysis. We observed a positive association with increasing years of smoking and cigarettes smoked and a negative association with smoking cessation. Excess weight was associated with increased risk, whereas exercise and consumption of nuts, vegetables, and fruits were associated with reduced risk. Blacks, Hispanics, and Asians had lower risk of AAA than whites and Native Americans. Well-known risk factors were reaffirmed, including male gender, age, family history, and cardiovascular disease. A predictive scoring system was created that identifies aneurysms more efficiently than current criteria and includes women, nonsmokers, and individuals aged <65 years. Using this model on national statistics of risk factors prevalence, we estimated 1.1 million AAAs in the United States, of which 569,000 are among women, nonsmokers, and individuals aged <65 years. Smoking cessation and a healthy lifestyle are associated with lower risk of AAA. We estimated that about half of the patients with AAA disease are not eligible for screening under current guidelines. We have created a high-yield screening algorithm that expands the target population for screening by including at-risk individuals not identified with existing screening criteria.
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            Risk factors for abdominal aortic aneurysm: results of a case-control study.

            Abdominal aortic aneurysms (AAAs) have historically been considered to be a manifestation of atherosclerosis. However, there are epidemiologic and biochemical differences between occlusive atherosclerotic disease and aneurysmal disease of the aorta. A case-control study was performed to investigate risk factors for AAA at the two tertiary care hospitals in Winnipeg, Manitoba, Canada, between June 1992 and December 1995 to investigate risk factors for AAA. Newly diagnosed cases of AAA (n = 98) were compared with non-AAA controls (n = 102), who underwent ultrasound for indications similar to those of the cases. Compared with that for never smokers, the adjusted odds ratio (OR) was 2.75 (95% confidence interval (CI): 0.85, 8.91) for 1-19 pack-years, 7.31 (95% CI: 2.44, 21.9) for 20-34 pack-years, 7.35 (95% CI: 2.40, 22.5) for 35-49 pack-years, and 9.55 (95% CI: 2.81, 32.5) for 50 or more pack-years. Other factors significantly associated with AAA were male gender (OR = 2.68, 95% CI: 1.26, 5.73), diastolic blood pressure (OR per 10 mmHg = 1.88, 95% CI: 1.31, 2.69), and family history of AAA (OR = 4.77, 95% CI: 1.26, 18.1). There was an inverse association between diabetes mellitus and AAA (OR = 0.32, 95% CI: 0.12, 0.88). Neither clinical hypercholesterolemia nor serum levels of total cholesterol, low density lipoprotein cholesterol, and high density lipoprotein cholesterol was associated with AAA. The results of this study suggest that the risk factors for AAA differ from those for atherosclerosis and that atherosclerosis per se is not an adequate explanation as the cause of AAAs.
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              HLA Class I and Class II Conserved Extended Haplotypes and Their Fragments or Blocks in Mexicans: Implications for the Study of Genetic Diversity in Admixed Populations

              Major histocompatibility complex (MHC) genes are highly polymorphic and informative in disease association, transplantation, and population genetics studies with particular importance in the understanding of human population diversity and evolution. The aim of this study was to describe the HLA diversity in Mexican admixed individuals. We studied the polymorphism of MHC class I (HLA-A, -B, -C), and class II (HLA-DRB1, -DQB1) genes using high-resolution sequence based typing (SBT) method and we structured the blocks and conserved extended haplotypes (CEHs) in 234 non-related admixed Mexican individuals (468 haplotypes) by a maximum likelihood method. We found that HLA blocks and CEHs are primarily from Amerindian and Caucasian origin, with smaller participation of African and recent Asian ancestry, demonstrating a great diversity of HLA blocks and CEHs in Mexicans from the central area of Mexico. We also analyzed the degree of admixture in this group using short tandem repeats (STRs) and HLA-B that correlated with the frequency of most probable ancestral HLA-C/−B and -DRB1/−DQB1 blocks and CEHs. Our results contribute to the analysis of the diversity and ancestral contribution of HLA class I and HLA class II alleles and haplotypes of Mexican admixed individuals from Mexico City. This work will help as a reference to improve future studies in Mexicans regarding allotransplantation, immune responses and disease associations.
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                Author and article information

                Contributors
                carlos.hinojosab@incmnsz.mx
                Journal
                BMC Med Genet
                BMC Med. Genet
                BMC Medical Genetics
                BioMed Central (London )
                1471-2350
                7 June 2019
                7 June 2019
                2019
                : 20
                : 102
                Affiliations
                [1 ]ISNI 0000 0001 0698 4037, GRID grid.416850.e, Department of Surgery, Section of Vascular Surgery and Endovascular Therapy, , Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubirán, ; Vasco De Quiroga 15, Tlalpan, Sección XVI, 14080 México City, Mexico
                [2 ]ISNI 0000 0001 2159 0001, GRID grid.9486.3, Universidad Nacional Autonoma de Mexico, Faculty of Medicine, Division for Postgraduate Studies, Master and Doctoral Degree Program, ; Mexico City, Mexico
                [3 ]ISNI 0000 0001 0698 4037, GRID grid.416850.e, Department of Transplant Surgery, Division of Immunogenetics, , Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubirán, ; Mexico City, Mexico
                [4 ]Centro Medico Nacional 20 de Noviembre, Biochemistry Unit, Mexico City, Mexico
                [5 ]ISNI 0000 0000 8515 3604, GRID grid.419179.3, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Biochemistry Unit, ; Mexico City, Mexico
                Author information
                http://orcid.org/0000-0002-9664-8703
                Article
                833
                10.1186/s12881-019-0833-8
                6555914
                31174489
                993c54ad-fc19-4705-8b61-ed4b976650e2
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 13 December 2018
                : 23 May 2019
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Genetics
                abdominal aortic aneurysms,hla-drb1,genetic risk,susceptibility,mexican population
                Genetics
                abdominal aortic aneurysms, hla-drb1, genetic risk, susceptibility, mexican population

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