The interleukin-1 cluster gene region is associated with multiple sclerosis in an Italian Caucasian population.
BACKGROUND
Polymorphisms of the interleukin-1 (IL-1) gene family have been proposed as potential variants for different diseases including multiple sclerosis (MS). With respect to MS, IL-1 beta (-511 C/T; rs16944), IL-1 beta (+3954 C/T; rs1143634), IL-1 alpha (-889 C/T; rs1800587), IL-1 alpha (+4845 G/T; rs17561), and the variable number of tandem repeats in intron 2 of the IL-1 receptor antagonist (IL-1RN) gene polymorphisms have been studied in different ethnic groups, leading to conflicting results.


METHODS
This study investigates the association between IL-1 genes and MS by means of 70 markers spanning the 1.1 Mb region where the IL-1 genes map and exploring both the linkage disequilibrium (LD) and the haplotype structure in a case-control design including 410 subjects (160 patients and 250 controls).


RESULTS
From allelic/genotypic tests, significant association was found for several polymorphisms including the IL-1 beta (-511 C/T) variant (P-adjusted = 4.5 x 10(-4)) and some polymorphisms around the IL-1RN gene. The 'block-step' pattern obtained from both the LD map and pairwise analysis identifies four LD regions. Region 1 showed a significant association with MS for the global test (P < 0.0001) and haplotypes containing the IL-1 beta (-511 C/T) variant still demonstrate highly significant association with disease (P-value range: 9.9 x 10(-5) to 0.02).


CONCLUSIONS
Our findings support the existence of a causative variant for MS within this candidate region in a representative Italian Caucasian population and, in particular, the role of the IL-1 beta (-511 C/T) variant warrants further investigation.
Borzani
I
I
Department of Biology and evolution, University of Ferrara, Ferrara, Italy.
Tola
M R
MR
Caniatti
L
L
Collins
A
A
De Santis
G
G
Luiselli
D
D
Mamolini
E
E
Scapoli
C
C
D000328:Adult; D016022:Case-Control Studies; D002874:Chromosome Mapping; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D007558:Italy; D008297:Male; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics*; D009103:Multiple Sclerosis / Q000208:ethnology / Q000235:genetics* / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044465:White People
D007375:Interleukin-1