The role of human host genetics in tuberculosis resistance

Kinnear, Craig; Hoal, Eileen G.; Schurz, Haiko; Helden, Paul D. van; Möller, Marlo

doi:10.1080/17476348.2017.1354700

Cited by 17 publications

(21 citation statements)

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“…17 In fact, there are several studies that support the association between vitamin D and bacterial infections, implicating polymorphisms in the VDR gene. [8][9][10][11] Nevertheless, there are presently only two reports on VDR polymorphisms and urinary tract infection. 8,18 The first, by Garcia-Nieto et al, 18 discarded the BsmI polymorphism as a candidate for a genetic biomarker in Spanish children with idiopathic hypercalciuria and urinary tract infection.…”

Section: Discussionmentioning

confidence: 99%

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OBJECTIVE:To evaluate the influence of the polymorphisms of the vitamin D receptor gene (FokI: rs2228570, BsmI: rs1544410, ApaI: rs7975232, and TaqI: rs731236) on the clinical parameters of patients with urinary tract infections. . The polymorphisms were detected through the polymerase chain reaction-restriction fragment length method in 119 patients diagnosed with urinary tract infection and in 206 individuals with no urinary tract infection. The data analysis was carried out using the c 2 and odds ratio (OR) with a 95% confidence interval (95%CI). The logistic regression method, adjusted by age and sex, was employed to evaluate the relation between clinical characteristics and genotypes, utilizing the STATA version 13.0 program. Statistical significance was set at a p<0.05. RESULTS:We found differences in the prevalence of the CA-ApaI genotype between the study groups. The FokI and BsmI polymorphisms and the TGAT and CGCT haplotypes were associated with certain clinical characteristics. CONCLUSIONS:A possible link between the vitamin D receptor gene and bacterial urinary tract infection in a Mexican population was suggested.Resumen OBJETIVO: Evaluar la influencia de los polimorfismos del gen del receptor de vitamina D (FokI: rs2228570, BsmI: rs1544410, ApaI: rs7975232 y TaqI: rs731236) en los parámetros clínicos de pacientes con infección de la vía urinaria. MATERIALES Y MÉTODOS:Estudio comparativo, prospectivo y transversal, llevado a cabo en el Hospital General de Culiacán Dr. Bernardo J. Gastélum, entre agosto de 2016 y julio de 2017. Los polimorfismos se detectaron mediante reacción en cadena de la polimerasa PCR. Para el análisis de los datos se utilizó la prueba de c 2 y la razón de probabilidades (OR), con intervalo de confianza de 95% (IC95%); con la intención de evaluar la relación entre las características clínicas y los genotipos se implementó la prueba de regresión logística ajustada por edad y sexo, con el programa STATAv13.0. Se consideró estadísticamente significativo el valor de p<0.05. RESULTADOS: El corte con enzimas de restricción se efectuó en 119 pacientes con diagnóstico de infección de la vía urinaria y en 206 individuos sin infección. Se encontraron diferencias en la prevalencia del genotipo CA-ApaI en ambos grupos de estudio. Los polimorfismos FokI y BsmI, y los haplotipos TGAT y CGCT se asociaron con algunas características clínicas. CONCLUSIONES: Se sugiere un posible vínculo entre el gen del receptor de vitamina D y las infecciones bacterianas de la vía urinaria en la población mexicana. PALABRAS CLAVES: Receptor de vitamina D; infección de la vía urinario; polimorfismos; haplotipos. artículo original Rev Mex Urol. 2018 noviembre-diciembre;78(6):419-24

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Section: Discussionmentioning

confidence: 99%

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“…Compared to the study of M. tuberculosis infection resistance, a larger number of investigations have been published addressing the genetic factors that protect against or predispose to developing clinical TB. Indeed, 11 TB GWAS have been done using clinical TB as phenotype [Table 1 , reviewed by ( 20 , 21 )]. Highlights included the identification of the 11p13 locus first identified in West Africa and replicated in Russia, Indonesia and South Africa ( 74 , 75 ), a large Icelandic GWAS which identified HLA class II variants which was weakly replicated in Russia and Croatia ( 79 ) and a recent GWAS of TB resistance in HIV positive individuals from hyperendemic TB regions in Uganda and Tanzania ( 78 ).…”

Section: Heritability Genetic Epidemiology and Population Geneticsmentioning

confidence: 99%

“…Since the publication of previous reviews of clinical TB GWAS ( 20 , 21 ), two additional studies have been completed using this study design. A three-stage replication approach was used in the Han Chinese and generated genotyping data (691 388 SNPs) for 972 TB cases and 1537 controls in the first stage ( 82 ).…”

Section: Heritability Genetic Epidemiology and Population Geneticsmentioning

confidence: 99%

“…The majority of studies made use of classical approaches employed by clinical genetics and genetic epidemiology (linkage and association studies), but these have encountered difficulties also faced by genetic investigations of other complex diseases. Three continuing challenges involve polygenicity, the definition of TB phenotypes and the collection of appropriately large study cohorts with carefully defined homogenous phenotypes ( 11 , 19 , 20 ). More recently functional genetic studies, including epigenetics, microRNAs and transcriptomics, have also shed light on the genetic basis of TB susceptibility ( 21 ).…”

Section: Introductionmentioning

confidence: 99%

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Genetic Resistance to Mycobacterium tuberculosis Infection and Disease

et al. 2018

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Natural history studies of tuberculosis (TB) have revealed a spectrum of clinical outcomes after exposure to Mycobacterium tuberculosis, the cause of TB. Not all individuals exposed to the bacterium will become diseased and depending on the infection pressure, many will remain infection-free. Intriguingly, complete resistance to infection is observed in some individuals (termed resisters) after intense, continuing M. tuberculosis exposure. After successful infection, the majority of individuals will develop latent TB infection (LTBI). This infection state is currently (and perhaps imperfectly) defined by the presence of a positive tuberculin skin test (TST) and/or interferon gamma release assay (IGRA), but no detectable clinical disease symptoms. The majority of healthy individuals with LTBI are resistant to clinical TB, indicating that infection is remarkably well-contained in these non-progressors. The remaining 5–15% of LTBI positive individuals will progress to active TB. Epidemiological investigations have indicated that the host genetic component contributes to these infection and disease phenotypes, influencing both susceptibility and resistance. Elucidating these genetic correlates is therefore a priority as it may translate to new interventions to prevent, diagnose or treat TB. The most successful approaches in resistance/susceptibility investigation have focused on specific infection and disease phenotypes and the resister phenotype may hold the key to the discovery of actionable genetic variants in TB infection and disease. This review will not only discuss lessons from epidemiological studies, but will also focus on the contribution of epidemiology and functional genetics to human genetic resistance to M. tuberculosis infection and disease.

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“…These individuals are more vulnerable to weakly virulent mycobacteria and they carry mutations interferon-gamma/interleukin 12 pathway genes [reviewed in Bustamante et al ( 2014 )]. The role of host genetic background in TB susceptibility has recently been reviewed (Kinnear et al 2017 ), therefore only highlights will be provided here.…”

Section: Host Genetic Susceptibility To Bacterial Infectionmentioning

confidence: 99%

Inter-individual variation in health and disease associated with pulmonary infectious agents

2018

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Respiratory infectious diseases resulting from bacterial or viral pathogens such as Mycobacterium tuberculosis, Streptococcus pneumoniae, respiratory syncytial virus (RSV), or influenza, are major global public health concerns. Lower respiratory tract infections are leading causes of morbidity and mortality, only behind ischemic heart disease and stroke (GBD 2015 LRI Collaborators in Lancet Infect Dis 17(11):1133–1161, 2017). Developing countries are particularly impacted by these diseases. However, while many are infected with viruses such as RSV (> 90% of all individuals are infected by age 2), only sub-populations develop severe disease. Many factors may contribute to the inter-individual variation in response to respiratory infections, including gender, age, socioeconomic status, nutrition, and genetic background. Association studies with functional single nucleotide polymorphisms in biologically plausible gene candidates have been performed in human populations to provide insight to the molecular genetic contribution to pulmonary infections and disease severity. In vitro cell models and genome-wide association studies in animal models of genetic susceptibility to respiratory infections have also identified novel candidate susceptibility genes, some of which have also been found to contribute to disease susceptibility in human populations. Genetic background may also contribute to differential efficacy of vaccines against respiratory infections. Development of new genetic mouse models such as the collaborative cross and diversity outbred mice should provide additional insight to the mechanisms of genetic susceptibility to respiratory infections. Continued investigation of susceptibility factors should provide insight to novel strategies to prevent and treat disease that contributes to global morbidity and mortality attributed to respiratory infections.

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The role of human host genetics in tuberculosis resistance

Cited by 17 publications

References 174 publications

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Genetic Resistance to Mycobacterium tuberculosis Infection and Disease

Inter-individual variation in health and disease associated with pulmonary infectious agents

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