CYP19A1 single nucleotide polymorphism associations with CYP19A1, NFκB1, and IL6 gene expression in human normal colon and normal liver samples

Figures & data

Table 1 Association of CYP19A1 expression and CYP19A1 SNPs in colon samples

SNPs	Frequency (n)	Median (2^ΔCt)	Fold change	P-value*
rs10459592
TT/TG	53	9.95E-05	4.7	0.042
GG	17	4.65E-04
rs1961177
CC	51	1.53E-04	1.8	0.040
CT/TT	19	8.37E-05
rs6493497
GG	53	1.53E-04	1.9	0.013
GA/AA	17	8.10E-05

Notes: rs1961177 and rs6493497 r²=1 among Caucasians and 0.58 among African-Americans.

* Nonparametric analysis of variance (Kruskal–Wallis or Wilcoxon rank sum test).

Abbreviation: SNPs, single nucleotide polymorphisms.

Table 2 Cross-associations of CYP19A1 genotypes with IL6 and NFκB1 gene expression in colon and liver samples

CYP19A1 SNPs	Frequency (n)	Median (2^ΔCt)	Fold change	P-value*
(A) NFκB1 expression in colon
rs12908960
GG/GA	65	0.079	2.0	0.047
AA	13	0.040
rs730154
AA	39	0.052	1.6	0.036
AG/GG	39	0.085
rs8025191
AA	51	0.085	1.7	0.051
AG/GG	27	0.050
rs17523880
CC	51	0.082	1.8	0.031
CA/AA	27	0.045
(B) IL6 expression in colon
rs11856927
TT/TG	61	0.0031	3.1	0.049
GG	16	0.0094
rs2470152
CC/CT	65	0.0033	3.7	0.025
TT	12	0.0121
rs2470144
GG	33	0.0023	3.4	0.047
GA/AA	44	0.0079
(C) IL6 expression in liver
rs12908960
GG	67	0.0149	3.5	0.004
GA/AA	106	0.0043
rs2470144
GG	66	0.0145	2.2	0.022
GA/AA	139	0.0066

Note:

* Nonparametric analysis of variance (Kruskal–Wallis or Wilcoxon rank sums test).

Abbreviations: IL6, interleukin-6; SNPs, single nucleotide polymorphisms; NFκB, nuclear factor kappa-light-chain-enhancer of activated B-cells.

Table 3 Association of haplotypes of CYP19A1 SNPs with selected gene expression in colon

CYP19A1 SNPs	Frequency	Median (2^ΔCt)	SD	P-value*
(A) CYP19A1 expression
rs10459592 T>G
rs1961177 C>T
rs6493497 G>A
Haplotype
TTA
0 copy†	0.80	1.8E-4	0.009	0.003
1 copy	0.20	4.8E-5	0.0002
(B) NFκB1 expression
rs12908960 G>A
rs730154 A>G
rs17523880 C>A
rs8025191 A>G
Haplotype
GGCA
0 copy	0.51	0.048	0.099	0.049
1 copy	0.37	0.085	0.134
2 copies	0.12	0.114	0.126
(C) IL6 expression
rs11856927 T>G
rs2470152 C>T
rs2470144 G>A
Haplotypes
TCG
0 copy	0.71	0.0078	0.151	0.011
1 copy	0.29	0.0019	0.018
GCG
0 copy	0.78	0.0047	0.123	0.053
1 copy	0.16	0.0014	0.010
2 copies	0.06	0.067	0.273

Notes: Haplotypes created based on results from colon samples;

* Nonparametric analysis of variance (Kruskal–Wallis or Wilcoxon rank sum test);

† 0 copy, no copies of the haplotype; 1 copy, one copy of the haplotype; 2 copies, two copies of the haplotype.

Abbreviations: IL6, interleukin-6; SNPs, single nucleotide polymorphisms; NFκB, nuclear factor kappa-light-chain-enhancer of activated B-cells; SD, standard deviation.

Table S1 Association of CYP19A1, NFκB1, and IL6 expression and CYP19A1, SNPs in colon samples

SNPs	Location	CYP19A1 expression P-value	NFκB1 expression P-value	IL6 expression P-value
CYP19A1 (15q21.1)
rs4275794	51501117	0.42	0.9971	0.0586
rs4646	51502844	0.64	0.6021	0.9072
rs2899472	51516055	0.77	0.5592	0.1061
rs700518	51529112	0.88	0.512	0.2037
rs17703883	51530097	0.39	0.4782	0.914
rs727479	51534547	0.93	0.6143	0.889
rs10459592	51536141	0.04	0.5134	0.1895
rs12591359	51539368	0.31	0.25	0.3854
rs12908960	51545860	0.47	0.0465	0.2858
rs7172156	51546298	0.66	0.17	0.2098
rs11856927	51548705	0.84	0.07	0.0487
rs2414099	51548782	0.68	0.2405	0.7202
rs17601876	51553909	0.82	0.8969	0.0814
rs2470158	51588395	0.99	0.11	0.3283
rs730154	51591204	0.32	0.0363	0.105
rs17523880	51592543	0.13	0.0309	0.9032
rs2470152	51594972	0.38	0.8373	0.0246
rs3751591	51606710	0.61	0.5042	0.687
rs1902584	51611654	0.08	0.7713	0.9128
rs2445762	51617708	0.16	0.07	0.9
rs2470144	51621725	0.39	0.6827	0.047
rs7174997	51622128	0.48	0.2621	0.9908
rs8025191	51623785	0.47	0.0514	0.836
rs1961177	51625078	0.04	0.5676	0.4442
rs6493497	51630835	0.01	0.2108	0.1595

Abbreviations: IL6, interleukin-6; SNPs, single nucleotide polymorphisms; NFκB, nuclear factor kappa-light-chain-enhancer of activated B-cells.

Table S2 Association of CYP19A1, NFκB1, and IL6 expression and CYP19A1 SNPs in liver samples

SNPs	CYP19A1 expression P-value	NFκB1 expression P-value	IL6 expression P-value
CYP19A1
rs10459592	0.885	0.081	0.088
rs11856927	0.019	0.182	0.374
rs12908960	0.326	0.456	0.004
rs17523880	0.071	,0.001	0.041
rs1902584	0.115	0.554	0.742
rs1961177	0.665	0.329	0.079
rs2470144	0.452	0.593	0.022
rs2470152	0.941	0.646	0.807
rs6493497	0.983	0.11	0.113
rs8025191	0.991	0.5	0.13

Abbreviations: SNPs, single nucleotide polymorphisms; IL6, interleukin-6; NFκB, nuclear factor kappa-light-chain-enhancer of activated B-cells.

Table S3 Association of haplotypes of CYP19A1 SNPs with selected gene expression in colon

CYP19A1 SNPs	Frequency	Median (2^ΔCT)	SD	P-value*
(A) CYP19A1 expression
rs10459592 T>G
rs1961177 C>T
rs6493497 G>A
Haplotype
GCG
0 copy	0.31	0.00120	0.00408	0.38
1 copy	0.50	0.00267	0.01049
2 copies	0.19	0.00070	0.00091
TCG
0 copy	0.40	0.00110	0.00364	0.72
1 copy	0.44	0.00303	0.01111
2 copies	0.16	0.00040	0.00052
TTA
0 copy	0.80	0.00227	0.00863	0.0038
1 copy	0.17	0.00011	0.00019
2 copies	0.03	0.00031	0.00028
(B) NFκB1 expression
rs12908960 G>A
rs730154 A>G
rs17523880 C>A
rs8025191 A>G
Haplotype
GGCA
0 copy	0.51	0.08794	0.09937	0.049
1 copy	0.37	0.12575	0.13461
2 copies	0.12	0.15026	0.12619
AACA
0 copy	0.60	0.09295	0.08635	0.09
1 copy	0.35	0.14648	0.15756
2 copies	0.05	0.04831	0.05116
GACA
0 copy	0.63	0.11540	0.12490	0.79
1 copy	0.34	0.09895	0.10657
2 copies	0.03	0.09522	0.10883
AAAG
0 copy	0.83	0.11841	0.12471	0.22
1 copy	0.15	0.06508	0.05379
2 copies	0.02	0.03880	0.0001
AAAA
0 copy	0.85	0.11301	0.12282	0.84
1 copy	0.15	0.08815	0.08215
(C) IL6 expression
rs11856927 T>G
rs2470152 C>T
rs2470144 G>A
Haplotype
TTG
0 copy	0.53	0.03375	0.10986	0.98
1 copy	0.43	0.05958	0.15508
2 copies	0.04	0.05123	0.08554
TCG
0 copy	0.71	0.6040	0.15092	0.025
1 copy	0.25	0.00934	0.01893
2 copies	0.04	0.00138	0.00166
GCA
0 copy	0.57	0.04007	0.10889	0.34
1 copy	0.38	0.04857	0.15764
2 copies	0.05	0.08305	0.14872
GCG
0 copy	0.77	0.04360	0.12301	0.053
1 copy	0.16	0.00644	0.00988
2 copies	0.07	0.16209	0.27339
TTA
0 copy	0.81	0.04673	0.13932	0.58
1 copy	0.19	0.04045	0.08229
TCA
0 copy	0.92	0.04811	0.13478	0.44
1 copy	0.08	0.01465	0.01784
GTG
0 copy	0.92	0.04869	0.13469	0.84
1 copy	0.08	0.00778	0.00644

Notes: Haplotypes created based on results from colon samples:

* non-parametric ANOVA (Kruskal–Wallis or Wilcoxon rank sums test).

Abbreviations: SNPs, single nucleotide polymorphisms; IL6, interleukin-6; NFκB, nuclear factor kappa-light-chain-enhancer of activated B-cells; SD, standard deviation.