The association between functional HLA-G 14 bp insertion/deletion and +3142 C > G polymorphisms and susceptibility to multiple sclerosis

- A significant increased frequencies of the +3142 G allele and the 14 bp DEL / +3142 G haplotype were found in MS patients compared to HD.
- MS patients with the +3142 C/C genotype have lower age of disease onset (ADO).
- The +3142 C > G polymorphism may constitute a genetic susceptibility factor to MS in the Tunisian population.
- No association was found between the two polymorphisms and sHLA-G serum levels.

We aimed to investigate two main polymorphisms in the 3′ untranslated region (3′UTR) of the HLA-G gene [14 bp insertion/deletion (INS/DEL) and +3142 C > G] and to assess their impact on the soluble HLA-G (sHLA-G) production in patients with multiple sclerosis (MS). This study included 60 patients with relasping-remitting (RR) MS and 112 healthy donors (HD). Mutations were identified by PCR and PCR-RFLP, and serum sHLA-G quantification was performed by ELISA. For the 14 bp INS/DEL polymorphism, variants frequencies were similar in patients and controls, whereas a significant increased frequency of the +3142 G allele was found in MS patients compared to HD (63.4% vs 52.3%, p = 0.04; OR = 1.58, 95%CI = 1.003-2.48). In addition, an association was found between MS susceptibility and the haplotypes regrouping both studied polymorphisms. Indeed, the 14 bp DEL/ + 3142 G haplotype frequency was significantly increased in MS patients compared to HD (20.8% vs 12.5%, p = 0.04, OR = 1.84). On the other hand, no associations were detected between both polymorphisms and clinical parameters, except the lower age of disease onset (ADO) in patients with the +3142 C/C genotype. Moreover, our study doesn't show any significant variation of sHLA-G serum levels between patients and controls. Our findings showed that the +3142 C > G, but not the 14 bp INS/DEL, polymorphism may constitute a genetic susceptibility factor to MS in the Tunisian population. However, no association was found between the two polymorphisms and sHLA-G serum levels.