Association between interleukin-6/6R gene polymorphisms and coronary artery disease in Russian population: influence of interleukin-6/6R gene polymorphisms on inflammatory markers

Figures & data

Table 1 Baseline characteristics of the study population

Variables	Controls (n=116)	Patients (n=198)	P
Age (years)	74.94±7.43	70.37±13.45	0.648
Gender (M/F)	33/83	109/89	0.000
BMI (kg/m^2)	30.33±6.09	30.71±2.75	0.543
Smoking (yes/no)	7/109	11/187	0.860
Hypertension (yes/no)	63/53	92/107	0.144
Type 2 diabetes mellitus (yes/no)	40/76	70/128	0.809
TC (mmol/L)	5.379±1.46	5.22±1.27	0.564
TG (mmol/L)	1.705±1.91	1.43±0.78	0.028
LDL-c (mmol/L)	3.294±1.24	2.94±0.93	0.250
HDL-c (mmol/L)	1.64±0.73	1.56±0.47	0.134
CA	2.28±0.41	2.34±0.35	0.331

Note: P-values <0.05 are shown in bold.

Abbreviations: CA, coefficient of atherogenicity; BMI, body mass index; F, female; HDL-c, high-density lipoprotein cholesterol; LDL-c, low-density lipoprotein cholesterol; M, male; TC, total cholesterol; TG, triglyceride.

Table 2 Genotype and allele frequencies of different cytokine SNPs in control and CAD patients and their association with CAD risk

Variables	Controls		Patients		OR (95% Cl)	P	pc
	n=116	%	n=198	%
IL-6
rs2069860
AA	109	96.46	190	99.48	1.0
AT	0	0	1	0.52	1.72 (0.069–42.73)	ns	ns
TT	4	3.54	0	0	0.064 (0.0034–1.198)	0.037	ns
Allele
A	218	96.46	381	99.74	1.0
T	8	3.54	1	0.26	0.072 (0.0089–0.576)	0.004	ns
rs13306435
AA	0	0	0	0	–
AT	8	7.02	6	3.03	2.42 (0.82–7.15)	0.18	ns
TT	106	92.98	192	96.97	1.0
Allele
A	8	3.5	6	1.5	2.36 (0.81–6.9)	0.18	ns
T	220	96.5	390	98.5	1.0
rs1800795
GG	32	27.6	62	31.3	1.0
GC	58	50	100	50.5	0.89 (0.52–1.52)	0.77	ns
CC	26	22.4	36	18.2	0.80 (0.44–1.46)	0.57	ns
Allele
G	122	52.6	224	56.6	1.0
C	110	47.4	172	43.4	0.85 (0.62–1.18)	0.38	ns
rs1800796
GG	104	89.7	182	91.9	1.0
GC	10	8.6	16	8.1	0.91 (0.40–2.09)	0.83	ns
CC	2	1.7	0	0	0.12 (0.0055–2.92)	0.34	ns
Allele
G	228	93.9	380	95.9	1.0
C	14	6.1	16	4.1	0.69 (0.329–1.43)	0.41	ns
IL-6R
rs2228044
GG	90	77.6	156	79.6	1.0
GC	26	22.4	40	20.4	0.95 (0.543–1.65)	0.96	ns
CC	0	0	0	0	–
Allele
G	206	88.8	352	89.8	1.0
C	26	11.2	40	10.2	0.90 (0.53–1.52)	0.79	ns
rs2228043
GG	0	0	0	0	–
GC	28	24.1	42	21.4	1.17 (0.67–2.013)	0.68	ns
CC	88	75.9	154	78.6	1.0
Allele
G	28	12.1	42	10.7	1.0
C	204	87.9	350	89.3	1.14 (0.69–1.90)	0.70	ns

Notes: P-values, Fisher’s exact test with Yates’s correction; pc-value, after Bonferroni correction. Bold values denote P<0.05.

Abbreviations: CAD, coronary artery disease; Cl, confidence level; IL, interleukin; ns, nonsignificant; OR, odds ratio; SNPs, single nucleotide polymorphisms.

Table 3 Differences between the control and patients with CAD, irrespective of their genotypes

Control vs CAD	P
IL-2	0.926
IL-4	0.170
IL-6	0.414
IL-8	0.000
IL-18	0.371
IL-1b	0.009
IL-10	0.135
Bilirubin	0.052
IFN-gamma	0.064
Nt-proBNP	0.050
Myoglobin	0.681
FABP	0.000
Troponin	0.279

Note: P-values <0.05 are shown in bold.

Abbreviations: CAD, coronary artery disease; FABP, fibrinogen and fatty acid-binding protein; IFN-gamma, interferon gamma; IL, interleukin; Nt-proBNP, N-terminal pro B-type natriuretic peptide.

Table 4 Interaction between different genotypes within IL-6/IL-6R gene SNPs in relation to cytokine and other CAD-associated clinical parameter concentrations in control and patients with diagnosed CAD

Examined parameters	rs1800795			rs1800796	rs2228044	rs2228043
	C/C ~ G/C P	C/C ~ G/G P	G/C ~ G/G P	G/C ~ G/G P	C/G ~ G/G P	C/C ~G/C P
Control subjects
IL-2	0.261	0.549	0.278	0.670	0.324	0.324
IL-4	0.087	0.239	0.469	0.337	0.076	0.076
IL-6	0.272	0.083	0.248	0.456	0.213	0.213
IL-8	0.719	0.282	0.256	0.278	0.262	0.262
IL-18	0.003	0.004	0.500	0.951	0.390	0.390
IL-1β	0.443	0.303	0.039	0.813	0.339	0.339
IL-10	0.969	0.300	0.099	0.387	0.822	0.822
Bilirubin	0.355	0.773	0.243	0.475	0.743	0.743
IFN-gamma	0.489	0.110	0.054	0.013	0.083	0.083
Nt-proBNP	0.835	0.754	0.987	0.012	0.008	0.008
Myoglobin	0.660	0.384	0.672	0.582	0.594	0.594
FABP	0.489	0.513	0.920	0.055	0.614	0.614
Troponin	0.479	0.303	0.393	0.287	0.281	0.281
	rs1800795	rs1800796	rs2228044	rs2228043
	C/C ~ G/G P	G/C ~ G/G P	C/G ~ G/G P	C/C ~ G/C P
Patients with diagnosed CAD
IL-2	0.021	0.049	0.516	0.696
IL-4	0.251	0.706	0.030	0.025
IL-6	0.067	0.949	0.250	0.182
IL-8	0.624	0.114	0.850	0.558
IL-18	0.804	0.888	0.440	0.519
IL-1β	0.717	0.508	0.736	0.636
IL-10	0.398	0.760	0.051	0.036
Bilirubin	0.126	0.679	0.131	0.105
IFN-gamma	0.514	0.734	0.432	0.577
Nt-proBNP	0.739	0.647	0.281	0.243
Myoglobin	0.286	0.532	0.282	0.808
FABP	0.343	0.641	0.921	0.525
Troponin	0.152	0.432	0.264	0.475

Note: P-values <0.05 are shown in bold.

Abbreviations: CAD, coronary artery disease; FABP, fibrinogen and fatty acid-binding protein; IFN gamma, interferon gamma; IL, interleukin; Nt-proBNP, N-terminal pro B-type natriuretic peptide; SNPs, single nucleotide polymorphisms.

Table 5 Logistic regression analysis for patients with CAD

Variables	P	OR (% 95 CI)
Gender	0.018	1.91 (1.16–2.98)
TG	0.026	2.57 (1.11–3.52)

Note: P-values <0.05 are shown in bold.

Abbreviations: CAD, coronary artery disease; CI, confidence interval; OR, odds ratio; TG, triglyceride.