Hepatitis C virus pharmacogenomics in Latin American populations: implications in the era of direct-acting antivirals

Figures & data

Figure 1 Limiting factors for the global access to DAAs in Latin America.

Abbreviations: DAAs, direct-acting antiviral agents; HCV, hepatitis C virus.

Table 1 Genetic factors related to HCV pharmacogenomics

NCBI dbSNP id	Location	Alleles	Associated with	References
rs368234815	IFNL4	TT	Spontaneous and/or PEG-IFN/RBV treatment-induced HCV clearance	^Citation33^–^Citation35, ^Citation40, ^Citation43
		ΔG	HCV persistence and/or PEG-IFN/RBV treatment failure
rs12979860	IFNL4	C	Spontaneous and/or PEG-IFN/RBV treatment-induced HCV clearance	^Citation2^–^Citation5, ^Citation32, ^Citation35^–^Citation42
		T	HCV persistence and/or PEG-IFN/RBV treatment failure
rs8099917	IFNL4	T	Spontaneous and/or PEG-IFN/RBV treatment-induced HCV clearance	^Citation2^–^Citation5, ^Citation32
		G	HCV persistence and/or PEG-IFN/RBV treatment failure
rs1127354	ITPA	A	Low risk of RBV-induced hemolytic anemia	^Citation47^–^Citation52
		C	High risk of RBV-induced hemolytic anemia
rs7270101	ITPA	C	Low risk of RBV-induced hemolytic anemia	^Citation47^–^Citation52
		A	High risk of RBV-induced hemolytic anemia

Abbreviations: HCV, hepatitis C virus; PEG-IFN/RBV, pegylated IFN-alpha plus ribavirin; SNP, single-nucleotide polymorphism.

Figure 2 IFNL4 SNP rs12979860.

Notes: Prevalence of the favorable (CC) and risk (CT/TT) genotypes of IFNL4 SNP rs12979860 in Bolivia (A, n=185), Peru (B, n=76), Paraguay (C, n=98), and the different geographic regions of Argentina: Central (D, n=991), Northwestern (E, n=250), Northeastern (F, n=260), Western (G, n=175), and Southern (H, n=115) areas. ^ap<0.05 when comparing samples from the Central region of Argentina with those from the Northeastern and Northwestern regions, Peruvians and Paraguayans; ^bp<0.0001 when comparing samples from the Central region of Argentina with Bolivians. Copyright ©2014. Nature Publishing Group. Adapted from Trinks J, Hulaniuk ML, Caputo M, et al. Distribution of genetic polymorphisms associated with hepatitis C virus (HCV) antiviral response in a multiethnic and admixed population. Pharmacogenomics J. 2014;14(6):549–554.⁷⁵ Adapted with permission from Trinks J, Hulaniuk ML, Caputo M, et al. Distribución de polimorfismos de nucleótido simple (SNPs) predictores de la respuesta al tratamiento antiviral en la infección crónica por el virus de la hepatitis C (HCV) en las distintas regiones geográficas de Argentina [Distribution of singlenucleotide polymorphisms (SNPs) predictive of antiviral treatment response in hepatitis C virus (HCV) chronic infection in different geographic regions in Argentina]. Medicina (B Aires). 2014;74 (Suppl 3):S117–S118. Spanish.⁷⁶
Abbreviation: SNP, single-nucleotide polymorphism.

Figure 3 ITPA SNP rs1127354.

Notes: Prevalence of the favorable (CA/AA) and risk (CC) genotypes of ITPA SNP rs1127354 in Bolivia (A, n=185), Peru (B, n=76), Paraguay (C, n=98), and the different geographic regions of Argentina: Central (D, n=991), Northwestern (E, n=250), Northeastern (F, n=260), Western (G, n=175), and Southern (H, n=115) areas. ^ap<0.05 when comparing samples from the Central region of Argentina with Peruvians and Paraguayans; ^bp<0.001 when comparing samples from the Central region of Argentina with those from the Northwestern region; ^cp<0.0001 when comparing samples from the Central region of Argentina with Bolivians. Copyright ©2014. Nature Publishing Group. Adapted from Trinks J, Hulaniuk ML, Caputo M, et al. Distribution of genetic polymorphisms associated with hepatitis C virus (HCV) antiviral response in a multiethnic and admixed population. Pharmacogenomics J. 2014;14(6):549–554.⁷⁵ Adapted with permission from Trinks J, Hulaniuk ML, Caputo M, et al. Distribución de polimorfismos de nucleótido simple (SNPs) predictores de la respuesta al tratamiento antiviral en la infección crónica por el virus de la hepatitis C (HCV) en las distintas regiones geográficas de Argentina [Distribution of singlenucleotide polymorphisms (SNPs) predictive of antiviral treatment response in hepatitis C virus (HCV) chronic infection in different geographic regions in Argentina]. Medicina (B Aires). 2014;74 (Suppl 3):S117–S118. Spanish.⁷⁶
Abbreviations: ITPA, inosine triphosphatase; SNP, single-nucleotide polymorphism.

Figure 4 ITPA SNP rs7270101.

Notes: Prevalence of the favorable (AC/CC) and risk (AA) genotypes of ITPA SNP rs7270101 in Bolivia (A, n=185), Peru (B, n=76), Paraguay (C, n=98), and the different geographic regions of Argentina: Central (D, n=991), Northwestern (E, n=250), Northeastern (F, n=260), Western (G, n=175), and Southern (H, n=115) areas. ^ap<0.05 when comparing samples from the Central region of Argentina with those from the Northeastern region; ^bp<0.0001 when comparing samples from the Central region of Argentina with those from the Northwestern region, Bolivians, and Peruvians. Copyright ©2014. Nature Publishing Group. Adapted from Trinks J, Hulaniuk ML, Caputo M, et al. Distribution of genetic polymorphisms associated with hepatitis C virus (HCV) antiviral response in a multiethnic and admixed population. Pharmacogenomics J. 2014;14(6):549–554.⁷⁵ Adapted with permission from Trinks J, Hulaniuk ML, Caputo M, et al. Distribución de polimorfismos de nucleótido simple (SNPs) predictores de la respuesta al tratamiento antiviral en la infección crónica por el virus de la hepatitis C (HCV) en las distintas regiones geográficas de Argentina [Distribution of singlenucleotide polymorphisms (SNPs) predictive of antiviral treatment response in hepatitis C virus (HCV) chronic infection in different geographic regions in Argentina]. Medicina (B Aires). 2014;74 (Suppl 3):S117–S118. Spanish.⁷⁶
Abbreviations: ITPA, inosine triphosphatase; SNP, single-nucleotide polymorphism.

Figure 5 Maternal ancestry.

Notes: Prevalence of the Native American and non-Native American mtDNA haplogroups in Bolivia (A, n=185), Peru (B, n=76), Paraguay (C, n=98), and the different geographic regions of Argentina: Central (D, n=991), Northwestern (E, n=250), Northeastern (F, n=260), Western (G, n=175), and Southern (H, n=115) areas. ^ap<0.005 when comparing samples from the Central region of Argentina with those from the Western and Northeastern regions; ^bp<0.0001 when comparing samples from the Central region of Argentina with those from the Northwestern region, Bolivia, Peru, and Paraguay. Copyright ©2014. Nature Publishing Group. Adapted from Trinks J, Hulaniuk ML, Caputo M, et al. Distribution of genetic polymorphisms associated with hepatitis C virus (HCV) antiviral response in a multiethnic and admixed population. Pharmacogenomics J. 2014;14(6):549–554.⁷⁵ Adapted with permission from Trinks J, Hulaniuk ML, Caputo M, et al. Distribución de polimorfismos de nucleótido simple (SNPs) predictores de la respuesta al tratamiento antiviral en la infección crónica por el virus de la hepatitis C (HCV) en las distintas regiones geográficas de Argentina [Distribution of singlenucleotide polymorphisms (SNPs) predictive of antiviral treatment response in hepatitis C virus (HCV) chronic infection in different geographic regions in Argentina]. Medicina (B Aires). 2014;74 (Suppl 3):S117–S118. Spanish.⁷⁶
Abbreviation: mtDNA, mitochondrial DNA.

Figure 6 Paternal ancestry.

Notes: Prevalence of the Native American and non-Native American Y-SNPs haplogroups in Bolivia (A, n=185), Peru (B, n=76), Paraguay (C, n=98), and the different geographic regions of Argentina: Central (D, n=991), Northwestern (E, n=250), Northeastern (F, n=260), Western (G, n=175), and Southern (H, n=115) areas. ^ap<0.05 when comparing samples from the Central region of Argentina with those from the Southern and Western regions; ^bp<0.01 when comparing samples from the Central region of Argentina with those from Paraguay; and ^cp<0.0001 when comparing samples from the Central region of Argentina with those from the Northwestern region, Bolivia, and Peru. Copyright ©2014. Nature Publishing Group. Adapted from Trinks J, Hulaniuk ML, Caputo M, et al. Distribution of genetic polymorphisms associated with hepatitis C virus (HCV) antiviral response in a multiethnic and admixed population. Pharmacogenomics J. 2014;14(6):549–554.⁷⁵ Adapted with permission from Trinks J, Hulaniuk ML, Caputo M, et al. Distribución de polimorfismos de nucleótido simple (SNPs) predictores de la respuesta al tratamiento antiviral en la infección crónica por el virus de la hepatitis C (HCV) en las distintas regiones geográficas de Argentina [Distribution of singlenucleotide polymorphisms (SNPs) predictive of antiviral treatment response in hepatitis C virus (HCV) chronic infection in different geographic regions in Argentina]. Medicina (B Aires). 2014;74 (Suppl 3):S117–S118. Spanish.⁷⁶
Abbreviation: Y-SNPs, Y-chromosome single-nucleotide polymorphisms.

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