Potential role of killer immunoglobulin receptor genes among individuals vaccinated against hepatitis B virus in Lebanon

Table 1 Demographics and characteristics of participants

	n	%
Gender (n = 101)
Male	39	38.6
Female	62	61.4
Age (yr) (n = 95)
19-29	38	40.0
30-39	19	20.0
40-49	17	17.9
50-59	11	11.6
60-69	6	6.3
70-79	2	2.1
80-89	2	2.1
Education (n = 99)
Illiterate	3	3.0
Primary School Education	3	3.0
Secondary School Graduate	9	9.1
High School Education	10	10.1
University Undergraduate Level	50	50.5
Others	24	24.2
Occupation (n = 99)
Student	15	15.2
Employed	74	74.7
Unemployed	7	7.1
Retired	3	3

Table 2 The observed and estimated killer immunoglobulin receptor gene frequencies in the study participants

	Inhibitory KIR								Non-inhibitory KIR						Pseudogene
	2DL1	2DL2	2DL3	2DL4	2DL5	3DL1	3DL2	3DL3	2DS1	2DS2	2DS3	2DS4	2DS5	3DS1	2DP1	3DP*001/002/004	3DP1*003
OF	99	56	84	100	42	96	100	100	40.6	55.4	46.5	95	34.7	41.6	99	17	100
KLF	0.9	0.34	0.6	1	0.24	0.8	1	1	0.23	0.33	0.27	0.78	0.19	0.24	0.9	1	1

2DL5A, 24.8%; 2DL5B, 28.7%; 2DS4*001/*002, 40.6%; 2DS4*003/007, 82.2%. KIR: Killer immunoglobulin receptor; OF: Observed frequency calculated by direct counting; KLF: Gene frequency calculated using the formula 1 - √ (1 - OF).

Table 3 Killer immunoglobulin receptor gene frequencies among study participants vaccinated against hepatitis B virus (protected and non-protected by hepatitis B vaccine) n (%)

KIR genes	Anti-HBsAg < 10 mIU/mL (n = 22)	Anti-HBsAg ≥ 10 mIU/mL (n = 52)	Test1	OR (95%CI)	P value
2DL2	14 (63.60)	27 (51.90)	0.858	0.62 (0.22-1.72)	0.446
2DL3	18 (81.80)	45 (86.40)	FET	1.43 (0.37-5.48)	0.723
2DL5A	8 (36.40)	13 (25.00)	0.982	0.58 (0.20-1.70)	0.4
2DL5B	5 (22.70)	19 (36.50)	1.346	1.97 (0.62-6.16)	0.289
2DS1	11 (50.00)	19 (36.50)	1.162	0.58 (0.21-1.58)	0.31
2DS2	14 (63.60)	26 (50.00)	1.157	0.57 (0.21-1.59)	0.318
2DS3	9 (40.90)	23 (44.20)	0.069	1.15 (0.42-3.15)	0.804
2DS4*001/002	8 (36.40)	20 (38.40)	0.029	1.09 (0.39-3.072)	1.00
2DS4*003/007	19 (86.40)	41 (78.85)	FET	0.59 (0.15-2.36)	0.534
2DS5	10 (45.50)	17 (32.60)	1.087	0.58 (0.21-1.62)	0.428
3DS1	11 (50.00)	21 (40.40)	0.582	0.68 (0.25-1.85)	0.608
3DP*001/002/004	6 (27.30)	9 (17.30)	FET	0.56 (0.17-1.82)	0.355

¹The statistical test performed to compare the frequencies of KIR gene expression among vaccinated and non-vaccinated study participants where by FET refers to Fisher’s exact test and the rest of the values represent the Pearson χ² value. We compared the frequencies of KIR genes with enough variability between study participants that were vaccinated against hepatitis B virus. The vaccinated participants were divided for this analysis into 2 groups depending on the level of anti-HBsAg. Anti-HBsAg < 10 mIU/mL, not protected against hepatitis B virus infection; anti-HBsAg ≥ 10 mIU/mL, protected against hepatitis B virus infection as a result of vaccination. KIR: Killer immunoglobulin receptor; FET: Fisher-exact test; HBsAg: Hepatitis B surface antigen. OR: Odds ratio.

Table 4 Killer immunoglobulin receptor gene frequencies among study participants vaccinated against hepatitis B virus as compared to non-vaccinated subjects n (%)

KIR genes	Vaccinated (n = 74)	Non-vaccinated (n = 25)	Test1	OR (95%CI)	P value
2DL2	41 (55.40)	15 (60.00)	0.161	0.83 (0.33-2.082)	0.436
2DL3	63 (85.10)	20 (80.00)	0.364	1.43 (0.44-4.62)	0.374
2DL5A	21 (28.40)	4 (16.00)	1.517	2.08 (0.64-6.79)	0.168
2DL5B	24 (32.40)	5 (20.00)	1.395	1.92 (0.64-5.73)	0.178
2DS1	30 (40.50)	10 (40.00)	0.002	1.02 (0.41-2.58)	0.577
2DS2	40 (54.10)	15 (60.00)	0.268	0.78 (0.31-1.97)	0.39
2DS3	32 (43.20)	14 (56.00)	1.223	0.60 (0.24-1.49)	0.191
2DS4*001/002	28 (37.80)	11 (44.00)	0.297	0.77 (0.31-1.94)	0.376
2DS4*003/007	60 (81.10)	22 (88.00)	FET	0.58 (0.15-2.23)	0.324
2DS5	27 (36.50)	7 (28.00)	0.597	1.47 (0.55-3.99)	0.302
3DS1	32 (43.20)	9 (36.00)	0.246	1.35 (0.53-3.46)	0.401
3DP*001/002/004	15 (20.30)	2 (8.00)	FET	2.92 (1.62-13.80)	0.134

We compared the frequencies of KIR genes with enough variability between study participants that were vaccinated against hepatitis B virus and those that were not.

¹The statistical test performed to compare the frequencies of KIR gene expression among vaccinated and non-vaccinated study participants whereby FET refers to Fisher’s exact test and the rest of the values represent the Pearson χ² value. KIR: Killer immunoglobulin receptor; FET: Fisher-exact test; OR: Odds ratio.

Table 5 The relationship between AA, AB and BB genotypes and the expression of killer immunoglobulin receptor genes among the study participants n (%)

KIR genes	AA (n = 44)	AB (n = 41)	BB (n = 16)	Test1	P value
2DL2	0 (0.00)	41 (100.00)	16 (100.00)	101	0.00a
2DL3	44 (100.00)	41 (100.00)	0 (0.00)	101	0.00a
2DL5A	10 (22.70)	10 (22.70)	5 (31.25)	FET	0.782
2DL5B	1 (2.27)	20 (24.39)	8 (50.00)	FET	0.00a
2DS1	16 (36.30)	18 (43.90)	7 (43.75)	0.579	0.749
2DS2	0 (0.00)	40 (97.50)	16 (100.00)	97.051	0.00a
2DS3	3 (6.80)	30 (73.17)	14 (87.50)	50.38	0.00a
2DS4*001/002	16 (36.40)	19 (37.50)	6 (37.50)	0.952	0.621
2DS4*003/007	38 (86.40)	31 (75.60)	14 (87.50)	FET	0.392
2DS5	14 (31.80)	16 (39.00)	5 (31.30)	0.584	0.747
3DS1	18 (40.90)	18 (43.90)	6 (40.00)	0.107	0.948
3DP*001/002/004	2 (4.50)	10 (24.40)	5 (31.30)	FET	0.0006a

¹The statistical test performed to determine the relationship between AA, AB and BB genotypes and the expression of KIR genes among vaccinated and non-vaccinated study participants. FET refers to the Fisher’s exact test and the rest of the values represent the Pearson χ² value.

^aP < 0.05, significant. KIR: Killer immunoglobulin receptor; FET: Fisher-exact test.

Table 6 Killer immunoglobulin receptor gene expression and levels of anti-HBs among the vaccinated study participants n (%)

KIR genes	Group I1 (n = 36)	Group II2 (n = 16)	Group III3 (n = 15)	Group IV4 (n = 7)	Test5	P value
2DL2	17 (47.20)	10 (62.50)	11 (73.30)	3 (42.90)	FET	0.362
2DL3	31 (86.10)	14 (87.50)	12 (80.00)	6 (85.70)	FET	0.824
2DL5A	9 (25.00)	4 (25.00)	4 (26.70)	4 (57.10)	FET	0.987
2DL5B	9 (25.00)	10 (62.50)	4 (26.70)	1 (14.30)	FET	0.0236
2DS1	11 (30.60)	8 (50.00)	7 (46.70)	4 (57.10)	FET	0.530
2DS2	16 (44.40)	10 (62.50)	11 (73.30)	3 (42.90)	FET	0.270
2DS3	12 (33.30)	11 (68.80)	8 (53.30)	1 (14.30)	5.01	0.060
2DS4*001/002	15 (41.70)	5 (31.30)	6 (40.00)	2 (28.60)	0.568	0.920
2DS4*003/007	28 (77.80)	13 (81.30)	13 (86.70)	6 (85.70)	FET	0.860
2DS5	11 (30.60)	6 (37.50)	6 (40.00)	3 (42.90)	0.846	0.850
3DS1	14 (38.90)	7 (43.80)	7 (46.70)	6 (85.70)	FET	0.960
2DL4	36 (100.00)	16 (100.00)	15 (100.00)	4 (57.10)	0.258	0.970
3DP*001/002/004	8 (22.20)	1 (6.30)	4 (26.70)	1 (14.30)	FET	0.420

¹Group I: Vaccinated participants and anti-HBs titers > 100 mIU/mL;

²Group II: Vaccinated participants and anti-HBs titers 10-100 mIU/mL;

³Group III: Vaccinated participants and anti-HBs titers 0.1-9.99 mIU/mL;

⁴Group IV: Vaccinated participants and anti-HBs titers = 0 mIU/mL;

⁵The statistical test performed to compare the frequencies of KIR gene expression among the vaccinated study participants whereby FET refers to Fisher’s exact test and the rest of the values represent the Pearson χ² value;

⁶Significant difference of KIR2DL5B expression among vaccinated study participants (P < 0.05). KIR: Killer immunoglobulin receptor; FET: Fisher-exact test.