Modic changes and interleukin 1 gene locus polymorphisms in occupational cohort of middle-aged men.
According to recent systematic reviews, Modic changes are associated with low-back pain. However, their pathophysiology remains largely unknown. A previous study of Northern Finnish males implicated that IL1A and MMP3 polymorphisms play a role in type II Modic changes. The purpose of the current study was to examine the association of IL1 cluster polymorphisms with Modic changes amongst middle-aged men in Southern Finland. The final study sample consisted of 108 men from three different occupations, who underwent magnetic resonance imaging (MRI) with a 0.1 T-scanner. Six single nucleotide polymorphisms (SNP) in the IL1 gene cluster (IL1A c.1-889C>T; IL1B c.3954C>T; IL1RN c.1812G>A; IL1RN c.1887G>C; IL1RN c.11100T>C; IL1RN c.1506G>A) were genotyped with the SNP-TRAP method or by allele-specific primer extension on modified microarray. In all, 45 subjects had Modic changes at one or more disc levels. The presence of the minor allele of IL1A (c.1-889C>T) was associated with these changes (any Modic change p = 0.031, type II changes p = 0.036). The carriers of the T-allele had a 2.5-fold risk of Modic change and the association was independent of the other IL1 gene cluster loci studied. In addition, a minor haplotype, with a frequency of 7.5% in the study population, including the minor alleles of IL1A c.1-889C>T, IL1RN c.1812G>A, and IL1RN c.1506G>A, was significantly associated with Modic changes. This observation is in accordance with the previous finding from a different geographical area, and thus confirms the importance of the IL1A gene in the pathophysiology of Modic changes.
Karppinen
Jaro
J
Finnish Institute of Occupational Health, Helsinki, Finland. jaro.karppinen@ttl.fi
Solovieva
Svetlana
S
Luoma
Katariina
K
Raininko
Raili
R
Leino-Arjas
Päivi
P
Riihimäki
Hilkka
H
D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D007403:Intervertebral Disc / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D055959:Intervertebral Disc Degeneration / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D017116:Low Back Pain / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D011110:Polymorphism, Genetic / Q000235:genetics*; D013131:Spine / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D013166:Spondylitis / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology
D015415:Biomarkers; D005819:Genetic Markers; D007375:Interleukin-1
Nat Rev Immunol. 2007 Jun;7(6):429-42
17525752
JAMA. 2001 Apr 11;285(14):1843-9
11308397
Rheumatology (Oxford). 2004 Jun;43 Suppl 3:iii10-iii16
15150427
Radiology. 2004 May;231(2):352-8
15064391
Pain. 2004 May;109(1-2):8-19
15082121
Spine (Phila Pa 1976). 2005 Dec 15;30(24):2735-42
16371896
Arthritis Rheum. 1999 Feb;42(2):366-72
10025932
Eur Spine J. 2008 Oct;17(10):1289-99
18751740
Spine (Phila Pa 1976). 2000 Jan;25(1):17-23
10647155
Spine (Phila Pa 1976). 2006 Apr 20;31(9):1026-31
16641780
Spine (Phila Pa 1976). 2000 Jan 15;25(2):166-9
10685479
J Bone Joint Surg Br. 2001 May;83(4):491-5
11380116
Spine (Phila Pa 1976). 1986 Mar;11(2):149-53
3704801
Eur Cytokine Netw. 2000 Jun;11(2):251-5
10903804
Epidemiology. 2004 Sep;15(5):626-33
15308963
Am J Physiol Heart Circ Physiol. 2005 May;288(5):H2031-41
15653761
Am J Hum Genet. 2001 Apr;68(4):978-89
11254454
Eur Spine J. 2006 Sep;15(9):1312-9
16896838
Spine (Phila Pa 1976). 1990 Feb;15(2):114-9
2326705
Spine (Phila Pa 1976). 2006 May 1;31(10):1143-8
16648751
Spine (Phila Pa 1976). 2008 May 15;33(11):1236-41
18469698
Skeletal Radiol. 2009 Mar;38(3):237-44
19096840
Spine (Phila Pa 1976). 2007 May 1;32(10):1129-34
17471097
Spine (Phila Pa 1976). 2000 Jul 1;25(13):1625-36
10870137
BMC Med Genet. 2008 Apr 28;9:38
18439317
Eur Spine J. 1998;7(5):363-8
9840468
Eur Spine J. 2008 Oct;17(10):1300-8
18648860
Arthritis Res Ther. 2007;9(4):R83
17760968
Eur Spine J. 2007 Jul;16(7):977-82
17334791
Arthritis Res Ther. 2005;7(4):R732-45
15987475
Arthritis Rheum. 2007 Oct 15;57(7):1311-5
17907216
Scand J Work Environ Health. 1998 Oct;24(5):358-66
9869307
Eur Radiol. 1999;9(6):1032-46
10415233
Spine (Phila Pa 1976). 2007 May 1;32(10):1116-22
17471095
Spine (Phila Pa 1976). 1994 Jan 15;19(2):138-42
8153819
Spine (Phila Pa 1976). 2007 Oct 1;32(21):E603-7
17906561
Radiology. 1988 Jan;166(1 Pt 1):193-9
3336678
Spine (Phila Pa 1976). 2005 May 15;30(10):1173-80
15897832
Spine (Phila Pa 1976). 2006 Jul 1;31(15):1714-8
16816768
Spine (Phila Pa 1976). 2007 Dec 1;32(25):2812-9
18246002
Spine (Phila Pa 1976). 2002 Dec 1;27(23):2631-44
12461389
Ann Rheum Dis. 1998 Feb;57(2):94-9
9613338
Pain. 2005 Mar;114(1-2):186-94
15733644
Science. 1999 Jul 16;285(5426):409-12
10411504
Eur Spine J. 2008 Nov;17(11):1407-22
18787845
Genome Res. 2000 Jul;10(7):1031-42
10899152
Spine (Phila Pa 1976). 1998 Dec 1;23(23):2477-85
9854746
Immunogenetics. 2002 May;54(2):82-6
12037600
Arthritis Rheum. 2009 Feb;60(2):470-81
19180518