Influence of Genetic Ancestry on INDEL Markers of NFKβ1, CASP8, PAR1, IL4 and CYP19A1 Genes in Leprosy Patients

Abstract

BackgroundLeprosy is an insidious infectious disease caused by the obligate intracellular bacteria Mycobacterium leprae, and host genetic factors can modulate the immune response and generate distinct categories of leprosy susceptibility that are also influenced by genetic ancestry.Methodology/Principal FindingsWe investigated the possible effects of CYP19A1 [rs11575899], NFKβ1 [rs28362491], IL1α [rs3783553], CASP8 [rs3834129], UGT1A1 [rs8175347], PAR1 [rs11267092], CYP2E1 [INDEL 96pb] and IL4 [rs79071878] genes in a group of 141 leprosy patients and 180 healthy individuals. The INDELs were typed by PCR Multiplex in ABI PRISM 3130 and analyzed with GeneMapper ID v3.2. The NFKβ1, CASP8, PAR1 and IL4 INDELs were associated with leprosy susceptibility, while NFKβ1, CASP8, PAR1 and CYP19A1 were associated with the MB (Multibacilary) clinical form of leprosy.Conclusions/Significance NFKβ1 [rs28362491], CASP8 [rs3834129], PAR1 [rs11267092] and IL4 [rs79071878] genes are potential markers for susceptibility to leprosy development, while the INDELs in NFKβ1, CASP8, PAR1 and CYP19A1 (rs11575899) are potential markers for the severe clinical form MB. Moreover, all of these markers are influenced by genetic ancestry, and European contribution increases the risk to leprosy development, in other hand an increase in African contribution generates protection against leprosy.

The CYP2B6 G516T polymorphism influences CD4 + T-cell counts in HIV-positive patients receiving antiretroviral therapy in an ethnically diverse region of the Amazon

“…24 Santos et al (2009) described the participation of Europeans (60%), native Indians (28%), and Africans (12%) in the foundation of the city of Belé m. 31 Recent studies have demonstrated that the genetic influence of ethnicity or ancestry might be related to variations in the genes involved in the individual's responses to certain diseases. 25,32 Therefore, the level of ethnic diversity present in the study population may influence the frequency of the CYP2B6 G516T polymorphism compared with different ethnic groups. The frequency of the polymorphic allele previously determined for individuals in the city of Belé m who were receiving treatment for tuberculosis (0.30) is similar to the frequency found in the present study (0.36).…”

“…[21][22][23] The Amazon region of Brazil is frequently characterized as an area that shows a variable and sometimes high degree of miscegenation among the Europeans, Africans, and native Indians, 24 a situation that clearly favors the variety of gene expression and the resistance or susceptibility to infectious agents and their associated diseases. 25 The presence of the CYP2B6 G516T polymorphism in HIV-1infected patients may promote the development of adverse reactions associated with antiretroviral agents. These reactions may compromise the treatment protocol in these individuals and cause an increase in the viral load and the selection of viruses with resistance mutations, thus limiting ART options.…”

Amerindian genetic ancestry as a risk factor for tuberculosis in an amazonian population

“…A number of studies in Brazil have also highlighted the importance of the role of ancestry in the susceptibility of a population to disease, including the study of Pinto et al [17], which identified a set of potential genetic markers related to susceptibility to leprosy, influenced in particular by AFR and EUR genomic ancestry. Carvalho et al [33] also found an association between AMR ancestry and an increased risk of developing acute lymphoblastic leukemia in the population of Brazilian Amazonia.…”

“…Genetic studies have indicated that populations of different ancestry, in particular AMR, may be relatively more susceptible to certain diseases than other populations [15][16][17][18]. In Mexican and Peruvian populations, for example, AMR ancestry was associated with increased risk for systemic lupus erythematosus [16].…”

“…In Mexican and Peruvian populations, for example, AMR ancestry was associated with increased risk for systemic lupus erythematosus [16]. In northern Brazil, AMR ancestry has been associated with susceptibility to the development of leprosy, including the severe clinical form [17], as well as an increased prevalence of hepatitis B and C [18], and an increased risk of developing acute lymphoblastic leukemia [15].…”