A polymorphism in the repetitive (TGGA)n sequence 5 ' to the human myelin basic protein gene in Italian multiple sclerosis patients

Human myelin basic protein (hMBP) gene is one of the candidate genes in the complex mosaic of multiple sclerosis (MS) susceptibility. In this study we verified the distribution of the polymorphism of the region 5' flanking th e first exon of the hMBP gene, in 97 relapsing remitting, 74 primary progre ssive Italian MS patients, and in 236 healthy controls, using polymerase ch ain reaction (PCR) and gel electrophoresis analysis in this region from 111 6 - 1540 nt. Three different band patterns were observed: one homozygote wi th a 354 bp long fragment, one homozygote with 424 bp long fragment and one heterozygote with both bands present. The short fragment was statistically more frequent in RRMS patients than in HC (P < 0.05). The long fragment wa s more present in HC. Similarly the short homozygous pattern (354 bp/354 bp ) was significantly higher in the RRMS patients versus the healthy controls (P < 0.01). The sequence analysis of the hMBP alleles showed that while th e long fragments matched the prototype sequence completely, all the short f ragments showed a deletion of 70 bp from nt 1177 to nt 1247, which explains the short 354 bp allele detected by PCR. Moreover two single mismatches in positions 1386 (T-->C) and 1431 (G-->A), were present only in the short hM BP fragment.