A Genetic Variant in the Interleukin 28B Gene As a Major Predictor for Sustained Virologic Response in Chronic Hepatitis C Virus Infection

Sixtos-Alonso, Ma. Sara; Avalos-Martinez, R.; Sandoval-Salas, R.; Dehesa-Violante, Margarita; García‐Juárez, Ignacio; Chavez-Ayala, Alejandro; Domínguez‐López, Aarón; Vargas-Voráckóva, Florencia; Toapanta‐Yanchapaxi, Liz; Amezcua-Guerra, Luís M.; Uribe, Misael; Sánchez-Ávila, Juan Francisco

doi:10.1016/j.arcmed.2015.07.001

Cited by 7 publications

(4 citation statements)

References 21 publications

(20 reference statements)

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“…Conversely, the Mestizos populations showed the highest prevalence of the respective C, G and TT alleles known to be associated with SC. These frequencies are consistent with those reported by others in Central Mexico, which are similar to Mexican-Americans and Caucasians [ 31 – 33 ]. Thus, given this pattern of genetic structure, it is plausible that this may also occur in other native and admixed groups throughout Latin America [ 34 ], although further studies are needed to evaluate this assumption.…”

Section: Discussionsupporting

confidence: 93%

Association with Spontaneous Hepatitis C Viral Clearance and Genetic Differentiation of IL28B/IFNL4 Haplotypes in Populations from Mexico

et al. 2016

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AimTo analyze the genetic heterogeneity of the Amerindian and admixed population (Mestizos) based on the IL28B (rs12979860, rs8099917) and IFNL4 (rs368234815) haplotypes, and their association with spontaneous clearance (SC) and liver damage in patients with hepatitis C infection from West Mexico.MethodsA total of 711 subjects from West Mexico (181 Amerindians and 530 Mestizos) were studied for the prevalence of IL28B (rs12979860C/T, rs8099917G/T) and IFNL4 (rs368234815∆G/TT) genotypes. A case-control study was performed in 234 treatment-naïve HCV Mestizos (149 chronic hepatitis C and 85 with SC) for the association of haplotypes with SC and liver damage. A real-time PCR assay was used for genotyping, and transitional elastography staged liver damage.ResultsSignificant Fst-values indicated differentiation between the studied populations. The frequencies of the protective C, T, TT alleles were significantly lower in the Amerindians than in Mestizos (p<0.05). The r2 measure of linkage disequilibrium was significant for all variants and the T/G/ΔG risk haplotype predominated in Amerindians and secondly in Mestizos. The protective C/T/TT haplotype was associated with SC (OR = 0.46, 95% IC 0.22–0.95, p = 0.03) and less liver damage (OR = 0.32, 95% IC 0.10–0.97, p = 0.04) in chronic patients. The Structure software analysis demonstrated no significant differences in ancestry among SC and chronic patients.ConclusionsWest Mexico´s population is genetically heterogeneous at the IL28B/IFNL4 polymorphisms. The T/G/ΔG high-risk haplotype predominated in Amerindians and the beneficial alternative haplotype in Mestizos. The C/T/TT haplotype was associated with SC and less liver damage in chronically infected Mestizo patients.

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Section: Discussionsupporting

confidence: 93%

Association with Spontaneous Hepatitis C Viral Clearance and Genetic Differentiation of IL28B/IFNL4 Haplotypes in Populations from Mexico

et al. 2016

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“…In our cohort of Mexican SLE patients, distribution of IFNL3/4 rs12979860 genotypes was similar to that reported in Mexican individuals infected with hepatitis C virus. 18 We found that in our patients with SLE this frequency is similar to those reported in European-American, African-American and Hispanic populations. 9 In SLE, the relevance of this high frequency of the C allele is that a significant number of patients may develop an overactivation of the IFN response, which could have an impact on their signaling pathway with enhanced activity of the Jak/STAT pathway and increased expression of IFN-stimulated genes, resulting in a high production of IFN-regulated chemokines including IP-10.…”

Section: Discussionsupporting

confidence: 89%

The presence ofIFL3/4rs12979860 C allele influences the in vitro IP-10 production by mononuclear cells from patients with systemic lupus erythematosus

Juárez-Vicuña

Pérez‐Ramos

Adalid‐Peralta

et al. 2020

Lupus

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Objective To explore whether the IFNL3/4 rs12979860 genotype may influence serum levels or production of interferon-inducible protein-10 (IP-10) by peripheral blood mononuclear cells from patients with systemic lupus erythematosus (SLE). Methods Sixty-six patients with SLE and 22 healthy blood donors (controls) were included. The IFNL3/4 rs12979860 polymorphism was genotyped by real-time polymerase chain reaction. IP-10 levels in sera supernatants of IFNα stimulated peripheral blood mononuclear cells were measured by enzime-linked immunosorbent assay. Results Allelic frequencies were CC (29%), CT (52%) and TT (20%) in SLE, and CC (32%), CT (41%) and TT (27%) in healthy controls. Median serum IP-10 levels were higher in SLE patients than in controls (190.8 versus 118.1 pg/ml; p < 0.001), particularly in those with high disease activity (278.5 versus 177.2 pg/ml; p = 0.037). However, serum IP-10 levels were not influenced by IFNL3/4 genotypes. Higher IP-10 production by peripheral blood mononuclear cells was found in both SLE patients (median 519.3 versus 207.6 pg/ml; p = 0.012) and controls (median 454.0 versus 201.7 pg/ml; p = 0.034) carrying the IFNL3/4 C allele compared with carriers of the T allele. Conclusions Although IFNL3/4 rs12979860 allele C does not appear to influence serum IP-10 levels in SLE, it plays an important role in the production of IP-10 by peripheral blood mononuclear cells after IFNα stimulation.

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“…Indeed, there are important differences in human leukocyte antigen (HLA) frequency between populations from Argentina and Mexico ( http://www.allelefrequencies.net ) that may result in different antigen recognition patterns among patients from these countries. In line with this, the prevalence of some protective alleles against infectious diseases of genes coding for HLA molecules or cytokines has been described to be very different in the Mexican population than other populations ( 38 , 39 ). Thus, it would be of interest to evaluate such features in our cohort of infected women to assess potential associations with their immune response and serological test performance.…”

Section: Discussionmentioning

confidence: 82%

Geographic Variations in Test Reactivity for the Serological Diagnosis of Trypanosoma cruzi Infection

Truyens

Dumonteil

Alger³

et al. 2021

J Clin Microbiol

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Chagas disease is a neglected disease caused by Trypanosoma cruzi parasites. Most of diagnosis is based on serological tests but the lack of a gold standard test complicates the measurement of test performance. To overcome this limitation, we used samples from a cohort of well-characterized T. cruzi infected women to evaluate the reactivity of two rapid diagnostic tests and one ELISA assay. Our cohort derived from a previous study on congenital transmission of T. cruzi , and consisted in 481 blood/plasma samples from Argentina (n=149), Honduras (n=228) and Mexico (n=104) with at least one positive T. cruzi PCR. Reactivity of the three tests ranged from 70.5% for the Wiener ELISA to 81.0% for the T-Detect and 90.4% for the Stat-Pak rapid tests. Test reactivity varied significantly among countries, and was highest in Argentina, and lowest in Mexico. When considering at least two reactive serological tests to confirm seropositivity, over 12% of T. cruzi infection cases from Argentina were missed by serological tests, over 21% in Honduras, and an alarming 72% in Mexico. Differences in test performance among countries were not due to differences in parasitemia, but differences in antibody levels against ELISA test antigens were observed. Geographic differences in T. cruzi parasite strains as well as genetic differences among human populations may both contribute to the discrepancies in serological testing. Improvements in serological diagnostics for T. cruzi infections are critically needed to ensure an optimum identification of cases.

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A Genetic Variant in the Interleukin 28B Gene As a Major Predictor for Sustained Virologic Response in Chronic Hepatitis C Virus Infection

Cited by 7 publications

References 21 publications

Association with Spontaneous Hepatitis C Viral Clearance and Genetic Differentiation of IL28B/IFNL4 Haplotypes in Populations from Mexico

Association with Spontaneous Hepatitis C Viral Clearance and Genetic Differentiation of IL28B/IFNL4 Haplotypes in Populations from Mexico

The presence ofIFL3/4rs12979860 C allele influences the in vitro IP-10 production by mononuclear cells from patients with systemic lupus erythematosus

Geographic Variations in Test Reactivity for the Serological Diagnosis of Trypanosoma cruzi Infection

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