A Mendelian randomized study on the correlation between 91 inflammatory protein levels and the risk of acute myeloid leukemia

doi:10.16150/j.1671-2870.2024.05.007

Abstract

Abstract:

Objective The study aims to analyze the correlation between circulating inflammatory proteins and the risk of acute myeloid leukemia (AML). Methods AML data were obtained from the FinnGen alliance as the outcome. The Genome-wide Association Studies (GWAS) data of 91 circulating inflammatory proteins were used as exposure factors. Mendelian randomization (MR) analysis was conducted to evaluate the effects of 91 circulating inflammatory proteins on the risk of AML. Inverse Variance Weighted (IVW) was used as the main analysis method, and the MR-Egger and Weighted Median (WM) methods were used to further strengthen the results. In addition, sensitivity analysis was used to evaluate the stability and reliability of the results. Results Among the 91 circulating inflammatory proteins, 8 were causally associated with the occurrence of AML (P<0.05). Specifically, higher levels of artemin (ARTN) (OR=0.458 3, 95% CI: 0.219 0-0.959 1), interleukin (IL)-2 receptor β (OR=0.2347, 95% CI: 0.094 1-0.585 3), sirtuin-2 (SIRT2) (OR=0.310 4, 95%CI: 0.138 0-0.698 2), and signal-transducing adaptor molecule binding protein (STAMPB) (OR=0.289 0, 95% CI: 0.104 9-0.796 1) were associated with a reduced risk of AML. In contrast, higher levels of CD6 (OR=3.269 3, 95% CI: 1.285 3-8.315 9), C-X-C motif chemokine ligand 5 (CXCL5) (OR=1.694 6, 95% CI: 1.013 4-2.833 6), IL-15 receptor α (OR=1.572 9, 95% CI: 1.050 0-2.344 8), and matrix metalloproteinase (MMP)-10 (OR=1.882 0, 95% CI: 1.061 4-3.337 1) were associated with an increased risk of AML. Sensitivity analysis using Cochran’s Q test (P>0.05) and MR-Egger regression test (P>0.05) showed no heterogeneity or pleiotropy in the single nucleotide polymorphisms (SNPs) of inflammatory proteins. Conclusions The Mendelian randomization study suggests that circulating inflammatory proteins ARTN, IL-2β, SIRT2, STAMPB, CD6, CXCL-5, IL-15α, and MMP-10 are causally associated with the risk of AML, which provides valuable insights for future research on the pathological mechanism of AML.

Key words: Acute myeloid leukemia, Mendelian randomization analysis, Genome-wide association study, Cellular immunotherapy

CLC Number:

AN Huihui, WU Tao, LIU Wenhui, TIAN Sirui. A Mendelian randomized study on the correlation between 91 inflammatory protein levels and the risk of acute myeloid leukemia[J]. Journal of Diagnostics Concepts & Practice, 2024, 23(05): 509-516.

Figures/Tables 4

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Exposure	Outcomes	SNPs	IVW			MR-Egger			Weighted median
Exposure	Outcomes	SNPs	SE	OR (95%CI)	P	SE	OR (95%CI)	P	SE	OR (95%CI)	P
ARTN	AML	14	0.3768	0.4583（0.2190-0.9591）	0.0384	0.8732	0.3252（0.0587-1.8007）	0.2226	0.5050	0.3688（0.1371-0.9922）	0.0482
CD6	AML	6	0.4763	3.2693(1.2853-8.3159)	0.0129	1.7673	2.4846(0.0778-79.3565)	0.6337	0.5444	3.1903(1.0975-9.2740)	0.0331
CXCL5	AML	11	0.2623	1.6946(1.0134-2.8336)	0.0443	0.3990	1.5728(0.7196-3.4377)	0.2857	0.2694	1.7337(1.0224-2.9397)	0.0411
IL-15RA	AML	9	0.2037	1.5729(1.0550-2.3448)	0.0262	0.3623	0.8618(0.4237-1.7531)	0.6937	0.2276	1.4059(0.9000-2.1962)	0.1344
IL-2RB	AML	11	0.4662	0.2347(0.0941-0.5853)	0.0019	0.9384	0.5465(0.0869-3.4385)	0.5357	0.6405	0.3298(0.0940-1.1573)	0.0833
MMP-10	AML	11	0.2922	1.8820(1.0614-3.3371)	0.0305	0.4725	1.6175(0.6407-4.0836)	0.3354	0.3657	1.7830(0.8707-3.6512)	0.1138
SIRT2	AML	11	0.4136	0.3104(0.1380-0.6982)	0.0047	0.8396	0.1697(0.0327-0.8798)	0.0638	0.5670	0.2611(0.0859-0.7935)	0.0179
STAMPB	AML	10	0.5171	0.2890(0.1049-0.7961)	0.0164	1.5349	0.2560(0.0126-5.1855)	0.4006	0.7170	0.2570(0.0630-1.0477)	0.0581

exposure	Outcomes	SNPs	Cochran’s Q test		MR-Egger intercept		MR-Presso
exposure	Outcomes	SNPs	IVW	MR Egger	Egger intercept	P	Global Test RSSobs	P
ARTN	AML	14	10.7366	10.5471	0.0349	0.6711	12.2728	0.6667
CD6	AML	6	1.4264	1.4004	0.0242	0.8797	0.9447	0.9447
CXCL5	AML	11	12.5723	12.4797	0.0170	0.8019	13.4745	0.4093
IL-15RA	AML	9	7.0478	3.0151	0.1516	0.0846	16.1052	0.4327
IL-2RB	AML	11	7.7765	6.6991	-0.1012	0.3264	9.3245	0.6887
MMP-10	AML	11	10.1907	9.9951	0.0315	0.6845	11.2204	0.5253
SIRT2	AML	11	10.4870	9.7401	0.0838	0.4276	12.7845	0.4190
STAMPB	AML	10	8.5948	8.5872	0.0148	0.9350	10.8371	0.4917