Prevalence of IFNL3 rs4803217 single nucleotide polymorphism and clinical course of chronic hepatitis C

doi:10.3748/wjg.v23.i21.3815

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World Journal of Gastroenterology

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World J Gastroenterol. Jun 7, 2017; 23(21): 3815-3824
Published online Jun 7, 2017. doi: 10.3748/wjg.v23.i21.3815

Table 1 Frequencies of alleles and genotypes of analyzed IFNL3 (IL28B) single nucleotide polymorphism in the group of patients enrolled (n = 196) n (%)

SNP	Allele frequency	Genotype frequency
rs4803217 (C/A)	C: 215 (54.85)	CC: 54 (27.55)
	A: 177 (45.15)¹	CA: 107 (54.59)
		AA: 35 (17.86)
rs12979860 (C/T)	C: 212 (54.08)	CC: 53 (27.04)
	T: 180 (45.92)¹	CT: 106 (54.08)
		TT: 37 (18.88)
rs8099917 (T/G)	T: 252 (64.29)	TT: 75 (38.27)
	G: 140 (35.71)¹	TG: 102 (52.04)
		GG: 19 (9.69)
rs12980275 (A/G)	A: 227 (57.91)	AA: 64 (32.65)
	G: 165 (42.09)¹	AG: 99 (50.51)
		GG: 33 (16.84)

¹MAF (minor allele frequency). SNP: Single nucleotide polymorphism.

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Table 2 Association between IFNL3 (IL28B) single nucleotide polymorphism and sustained virological response after pegylated interferon alpha and ribavirin treatment in chronic hepatitis C patients

SNP	Allele/genotype	Response (n = 54), n (%)	Non-response (n = 126), n (%)	Response vs non-response	OR_crude (95%CI)/OR_adjusted (95%CI)¹	P_crude/P_adjusted¹
rs4803217 (C/A)	C/A	85 (78.70)/23 (21.30)	109 (43.25)/143 (56.75)	C/A	4.848 (2.871-8.186)	< 0.0001^a
	CC	34 (62.96)	14 (11.11)	CC/CA + AA	13.6 (6.219-29.770)/8.357 (3.013-23.181)	< 0.0001^a/< 0.0001^a
	CA	17 (31.48)	81 (64.29)	CC + CA/AA	5.547 (1.617-19.035)/3.240 (0.849-12.367)	0.003^a/0.082
	AA	3 (55.56)	31 (24.60)	Dose of C allele	7.588 (3.858-14.922)/4.310 (1.956-9.500)	< 0.0001^a/0.0002^a
rs12979860 (C/T)	C/T	82 (75.93)/26 (24.07)	108 (42.86)/144 (57.14)	C/T	4.205 (2.533-6.980)	< 0.0001^a
	CC	32 (59.26)	14 (11.11)	CC/CT + TT	11.636 (5.351-25.306)/9.765 (3.407-27.990)	< 0.0001^a/< 0.0001^a
	CT	18 (33.33)	80 (63.49)	CC + CT/TT	4.255 (1.424-12.715)/4.413 (0.927-21.011)	0.006^a/0.059
	TT	4 (7.41)	32 (25.40)	Dose of C allele	6.072 (3.195-11.538)/5.574 (2.345-13.246)	< 0.0001^a/< 0.0001^a
rs8099917 (T/G)	T/G	80 (74.07)/28 (25.93)	149 (59.13)/103 (40.87)	T/G	1.975 (1.2-3.251)	0.007^a
	TT	29 (53.70)	39 (30.95)	TT/TG + GG	2.588 (1.344-4.981)/2.097 (0.844-5.210)	0.004^a/0.107
	TG	22 (40.74)	71 (56.35)	TT + TG/GG	2.473 (0.690-8.867)/2.397 (0.482-11.926)	0.153/0.280
	GG	3 (5.56)	16 (12.70)	Dose of T allele	2.190 (1.266-3.788)/1.869 (0.911-3.837)	0.0048^a/0.0845
rs12980275 (A/G)	A/G	85 (78.70)/23 (21.30)	120 (47.62)/132 (52.38)	A/G	4.065 (2.410-6.857)	< 0.0001^a
	AA	35 (64.81)	23 (18.25)	AA/AG + GG	8.249 (4.021-16.923)/5.225 (1.999-13.658)	< 0.0001^a/0.001^a
	AG	15 (27.78)	74 (58.73)	AA + AG/GG	3.737 (1.244-11.223)/4.075 (0.848-19.589)	0.013^a/0.076
	GG	4 (7.41)	29 (23.02)	Dose of A allele	4.705 (2.591-8.542)/3.596 (1.659-7.791)	< 0.0001^a/0.001^a

¹Adjusted for staging;

^aP < 0.05. SNP: Single nucleotide polymorphism.

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Table 3 Multivariate analysis of factors associated with outcome of chronic hepatitis C treatment with pegylated interferon alpha and ribavirin

Variable	OR (95%CI)	P value
Response (SVR)¹
rs4803217 (C/A)	4.979 (1.344-18.444)	0.016^a
rs12979860 (C/T)	1.499 (0.446-5.042)	0.510
rs8099917 (T/G)	0.594 (0.247-1.429)	0.242
rs12980275 (A/G)	1.658 (0.598-4.594)	0.328
Stage of fibrosis	3.278 (1.108-9.698)	0.031^a
Relapse²
rs4803217 (C/A)	0.134 (0.023-0.789)	0.024^a
rs12979860 (C/T)	2.381 (0.444-12.773)	0.303
rs12980275 (A/G)	1.046 (0.369-2.961)	0.932

¹Model summary: χ² (5) = 56.028; P < 0.0001, constant: < 0.0001. rs4803217, rs12979860, rs8099917, rs12980275 (dose allele model) an stage of fibrosis were included in the analysis;

²Model summary: χ² (3) = 12.337, P < 0.00632, constant: P = 0.019. rs4803217, rs12979860, and rs12980275 (dose allele model) were included in the analysis.

^aP < 0.05 (independent factors). SVR: Sustained virological response.

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Table 4 Association of IFNL3 (IL28B) rs4803217 and rs8099917 combined genotypes with response to pegylated interferon alpha and ribavirin treatment

Genotypes/combined genotypes	SVR (n = 54), n	Non-response (n = 126), n	OR (95%CI)	P value
rs4803217CC/rs8099917TT	22	13	0.697 (0.276-1.759)	0.442
rs4803217CC/rs8099917TG	12	1	4.941 (0.586-41.699)	0.156
rs4803217CC¹	34	14	Ref.	-
rs4803217CA/rs8099917TT	5	9	2.813 (0.832-9.504)	0.136
rs4803217CA/rs8099917TG	9	71	0.641 (0.267-1.542)	0.388
rs4803217CA/rs8099917GG	2	1	10.125 (0.865-118.471)	0.083
rs4803217CA	16	81	Ref.	-
rs4803217AA/rs8099917TT	1	2	5.167 (0.355-75.138)	0.298
rs4803217AA/rs8099917TG	1	14	0.738 (0.070-7.736)	1.000
rs4803217AA/rs8099917GG	1	15	0.689 (0.066-7.192)	1.000
rs4803217AA	3	31	Ref.	-

¹Combination of rs4803217CC and rs8099917GG genotypes was not observed. SNP: Single nucleotide polymorphism; SVR: Sustained virological response.

Full Size Table

Table 5 Association between IFNL3 (IL28B) gene single nucleotide polymorphism and relapse after pegylated interferon alpha and ribavirin treatment in chronic hepatitis C patients

SNP	Allele/genotype	Relapse (n = 39), n (%)	Non-relapse (n = 38), n (%)	Relapse vs non-relapse	OR (95%CI)	P value
rs4803217 (C/A)	C/A	38 (48.72)/40 (51.28)	56 (73.68)/20 (26.32)	C vs A	0.339 (0.173-0.667)	0.001^a
	CC	7 (17.95)	21 (55.26)	CC vs CA + AA	0.177 (0.063-0.500)	0.0007^a
	CA	24 (61.54)	14 (36.84)	CC + CA vs AA	0.332 (0.081-1.364)	0.113
	TT	8 (20.51)	3 (7.89)	Dose of C allele	0.296 (0.134-0.653)	0.002^a
rs12979860 (C/T)	C/T	40 (51.28)/38 (48.72)	52 (68.42)/24 (31.58)	C vs T	0.486 (0.252-0.937)	0.030^a
	CC	8 (20.51)	18 (47.37)	CC vs CT + TT	0.287 (0.105-0.783)	0.013^a
	CT	24 (61.54)	16 (42.11)	CC + CT vs TT	0.538 (0.143-2.013)	0.351
	TT	7 (17.95)	4 (10.53)	Dose of C allele	0.442 (0.211-0.925)	0.028^a
rs8099917 (T/G)	T/G	56 (71.79)/22 (28.21)	52 (68.42)/24 (31.58)	T vs G	1.175 (0.589-2.344)	0.647
	TT	21 (53.85)	17 (44.74)	TT vs TG + GG	1.304 (0.526-3.233)	0.566
	TG	14 (35.90)	18 (47.37)	TT + TG vs GG	0.750 (0.156-3.560)	1.000
	GG	4 (10.26)	3 (7.89)	Dose of T allele	1.174 (0.582-2.365)	0.649
rs12980275 (A/G)	A/G	45 (57.69)/33 (42.31)	56 (73.68)/20 (26.32)	A vs G	0.487 (0.247-0.961)	0.037^a
	AA	12 (30.77)	22 (57.89)	AA vs AG + GG	0.323 (0.127-0.825)	0.017^a
	AG	21 (53.85)	12 (31.58)	AA + AG vs GG	0.647 (0.167-2.503)	0.737
	GG	6 (15.38)	4 (10.53)	Dose of A allele	0.495 (0.245-0.998)	0.046^a

^aP < 0.05. SVR: Sustained virological response.

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Citation: Świątek-Kościelna B, Kałużna E, Strauss E, Nowak J, Bereszyńska I, Gowin E, Wysocki J, Rembowska J, Barcińska D, Mozer-Lisewska I, Januszkiewicz-Lewandowska D. Prevalence of IFNL3 rs4803217 single nucleotide polymorphism and clinical course of chronic hepatitis C. World J Gastroenterol 2017; 23(21): 3815-3824
URL: https://www.wjgnet.com/1007-9327/full/v23/i21/3815.htm
DOI: https://dx.doi.org/10.3748/wjg.v23.i21.3815