Different Allele Frequency between Males and Females of a SNP of the Human Beta T Cell Receptor

We studied a single nucleotide polymorphism (SNP) located in the human beta T-cell receptor, in association studies and different allele frequency in the two sexes. Here we report a new series of 200 subjects (100 males and 100 females) in a restricted age range, 20-30 years. We found the following results: in males 57/100 (57%) were heterozygous, 26/100 (26%) were homozygous for the two digestion fragments and 17/100 (17%) were homozygous for the 603bp fragment. Females were 44/100 (44%) heterozygous, 24/100 (24%) homozygous for the two digestion fragments and 32/100 (32%) homozygous for the 603bp fragment. The allele frequency was significantly different according to chi square analysis (X square statistic (df = 2) = 7.412; p = 0.025). Our study shows that in females, but not in males , there is a significant increase of CC homozygous status and a proportionate decrease of heterozygous status compared with Hardy-Weinberg expectations. This study could explain the controversial results obtained by association studies between this SNP (rs1800907) and autoimmune diseases made in the ninety and uncorfirmed in more recent papers. Moreover it could be a starting point to search for other autosomical DNAs diffences between the two sexes

T-cell receptor polymorphism in primary biliary cirrhosis

T-cell receptor (TCR) plays a key role in immune regulation and polymorphisms of its genes have been found in association with several autoimmune diseases. No data are available for primary biliary cirrhosis, an autoimmune liver disease the natural history of which is highly variable. We studied a TCR constant beta-2 chain polymorphism in 70 patients affected by primary biliary cirrhosis and in 70 healthy controls. The DNA chains of patients and controls were amplified by means of polymerase chain reaction using primers designed around a Bgl II polymorphic restriction site and digested for restriction fragment length polymorphism analysis. We found a slight increase of the heterozygous genotype in patients compared with controls (49 vs 40%), which became higher if only patients with early disease were considered (60 vs 40%). Heterozygous patients had less severe disease as indicated by a lower Mayo score (5.1 +/- 1.2 vs 5.7 +/- 1.2 in non-heterozygous). Our data suggest that TCR constant beta-2 polymorphism does not play a key role in modulating the multifactorial etiopathogenesis of primary biliary cirrhosis

Chromosome 7 monosomy and deletions in myeloproliferative diseases

We studied deletion and monosomy of chromosome 7 in 150 patients with myeloproliferative diseases. We found 8/150 patients with monosomy 7 by cytogenetics and 4/150 with deletions of the long arm of chromosome 7 by restriction fragment length polymorphism (RFLP) analysis performed with Southern and polymerase chain reaction. To overcome limitation of RFLP analysis, we restricted loss of heterozygosity study with microsatellites to 45 patients, observing deletion 7q31.1 in 7/45 patients. In all patients with molecular alterations the deletion was observed only in myeloid cells, while the monosomy was detected in both myeloid precursor and lymphocytes. This finding suggests a CD34-totipotent stem cell origin for the monosomy and a colony forming unit - granulocyte, erythrocyte, monocyte, megakaryocytes (CFU-GEMM) stem cell origin for the deletions