title: High frequency of TNF alleles -238A and -376A in individuals from northern Sardinia.
abstract: The G to A single nucleotide polymorphisms (SNPs), at position -376, -308 and -238 in the promoter of the tumor necrosis factor alpha (TNF) gene, have been independently correlated with numerous diseases. Alleles TNF(-376A) and TNF(-238A) are normally found throughout the world with very low frequencies. We investigated the frequency of these SNPs in Sicilian subjects hospitalized after traumatic brain injury and in three groups of subjects from northern Sardinia: healthy subjects and individuals with multiple sclerosis or ischemic stroke. While no significant difference was found between healthy and disease subjects, the frequency of TNF(-376A) and TNF(-238A) was elevated up to 10 times in Sardinia compared to Sicily and other populations throughout the world. These elevated frequencies may be the result of genetic drift or of selective pressure on TNF itself or on neighboring genes, including the HLA. Malaria, endemic to Sardinia until the end of the 1940s, and the bubonic plague, are among the possible causes of selection. These findings indicate that Sardinia is an ideal location to further elucidate the correlation between TNF or HLA polymorphisms and diseases, including multiple sclerosis and type-I diabetes, present with an unusually high frequency and co-morbidity in Sardinia.
authors.affiliation: The Harold L. Dorris Neurological Research Center, Department of Neuropharmacology, The Scripps Research Institute, 10550 North Torrey Pines Road, SR307, La Jolla, CA 92037, USA.
authors.forename: Sebastian A
authors.initials: SA
authors.lastname: Wirz
authors.forename: Maria C
authors.initials: MC
authors.lastname: Morale
authors.forename: Bianca
authors.initials: B
authors.lastname: Marchetti
authors.forename: Alasdair M
authors.initials: AM
authors.lastname: Barr
authors.forename: Stefano
authors.initials: S
authors.lastname: Sotgiu
authors.forename: Giulio
authors.initials: G
authors.lastname: Rosati
authors.forename: Maura
authors.initials: M
authors.lastname: Pugliatti
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Sanna
authors.forename: Orazio
authors.initials: O
authors.lastname: Giliberto
authors.forename: Tamas
authors.initials: T
authors.lastname: Bartfai
authors.forename: Bruno
authors.initials: B
authors.lastname: Conti
mesh_terms: D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D005787:Gene Frequency; D006801:Humans; D007558:Italy; D009103:Multiple Sclerosis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D020521:Stroke / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha