ABSTRACT
In this case-control study, 68 relapsing-remitting multiple sclerosis (RRMS) patients and 133 control were genotyped for IL1A-889 (rs1800587), IL1B-511 (rs16944), IL1B+3962 (rs1143634), IL1R1pst11970 (rs2234650) and IL1RNmspa1 11,100 (rs315952) variants. Sequence-specific-primer-polymerase-chain-reaction was the genotyping method. Logistic regression analysis demonstrated protective effects of IL1B-511, IL1R1pst11970 and IL1RNmspa1 11,100 against MS incidence, while no association was found with IL1A-889 and IL1B+3962 variants. Allele frequencies showed no significant gender, medication or expanded disability status scale-associated variation. Haplotype analysis suggested 4.31-fold increased odds for MS in subjects with C-T-C-C-T haplotype of the respective loci. In conclusion, IL-1 gene variants influence MS susceptibility in Iraqi population.
ABSTRACT
Multiple sclerosis (MS) is a neurodegenerative autoimmune disease, in which cytokines play a prominent role. Among these cytokines are interleukin-4 (IL-4) and IL-10, which have been demonstrated to be involved in immunopathogenesis of the disease. The present case-control study inspected the association between seven single nucleotide polymorphisms (SNPs) of IL4 (IL4-1098: rs2243248, IL4-590: rs2243250, and IL4-33: rs2070874), IL4RA (IL4RA+1902: rs1801275), and IL10 (IL10-1082: rs1800896, IL10-819: rs1800871, and IL10-592: rs1800872) genes and MS in Iraqi patients. Sixty-eight clinically definite relapsing-remitting MS Iraqi patients and 158 age- and gender-matched healthy control subjects were enrolled in the study. The SNPs were detected by the PCR-SSP (polymerase chain reaction-sequence specific primer) method. Results revealed that only IL4-1098, IL4-590, IL4-33, and IL10-592 SNP allele and/or genotype frequencies showed a significant variation between MS patients and control. At the haplotype level, the estimated frequency of TCC (IL4-1098-IL4-590-IL4-33) and GCC (IL10-1082-IL10-819-IL10-592) haplotypes was significantly increased in patients compared to control (TCC: 63.2 vs. 48.0%; odds ratio = 2.81; 95% confidence interval = 1.86-4.25; pc = 5.0 × 10-6; GCC 39.0 vs. 22.2%; odds ratio = 2.24; 95% confidence interval = 1.45-3.46; pc = 0.002). In conclusion, IL4 and IL10 genes harbor important SNPs that may confer MS susceptibility. In addition, their role in reducing the risk of disease is also suggested. However, the susceptibility of the investigated role can be better evaluated in terms of haplotype frequencies.
Subject(s)
Genetic Predisposition to Disease/genetics , Interleukin-10/genetics , Interleukin-4/genetics , Multiple Sclerosis/genetics , Adult , Case-Control Studies , Female , Humans , Iraq , Male , Polymorphism, Single NucleotideABSTRACT
In this report, 224 unrelated healthy Iraqi Arabs (102 males and 122 females) were genotyped for 22 SNPs (single nucleotide polymorphisms) belong to 13 cytokine genes (IL1A, IL1B, IL1RA, IL1R, IL2, IL4, IL4R, IL6, IL10, IL12, IFNG, TNFA and TGFB1). The method of detection was PCR-SSP (polymerase chain reaction-sequence specific primer). The data were presented in terms of allele and genotype frequencies. Two-locus haplotype frequencies were also estimated for some SNPs. Genotype frequencies of detected cytokine gene polymorphisms are available in the Database of Allele Frequencies Net under the AFND number 3422 and the population name "Iraq Arab Cytokine".
