title: E148Q MEFV mutation carriage and longevity in individuals of Ashkenazi origin.
abstract: The high carriage rate of MEFV mutations in at risk populations suggests that they confer a selective advantage, possibly by way of protection from infections. Here, we sought to assess whether this putative protection contributes to longevity, by studying MEFV mutation status in nonagenarians and the association of mutation carriage with life-threatening conditions. DNA samples and a medical history questionnaire were obtained from 200 nonagenarians (>90 years of age), who received medical treatment at a large tertiary hospital in Israel. The prevalence of MEFV mutations in the study group was compared to the known prevalence, by ethnic group, in the Israeli population. The presence of associated diseases in mutation carriers versus noncarriers was compared. The majority of study subjects were females (67.5 %) of Ashkenazi origin (78%). A fifth carried an MEFV mutation, most commonly E148Q (73% of total mutations), followed by V726A (5%). Only the frequency of E148Q in Ashkenazi subjects was found to be higher than expected in the general Ashkenazi population (19.8 vs. 2.6%, p < 0.0001). Cardiac arrhythmias and hypothyroidism were more common in mutation carriers, while no difference was noted, between carriers and noncarriers, in the rates of ischemic heart disease, diabetes, stroke and a wide range of other serious conditions. Our findings suggest that E148Q carriage contributes to longevity in the Ashkenazi population, perhaps by enhancing resistance to infections.
authors.affiliation: Medicine F and Heller Institute of Medical Research, Sheba Medical Center, Tel-Hashomer, Israel. merav.lidar@gmail.com
authors.forename: Merav
authors.initials: M
authors.lastname: Lidar
authors.forename: Yael
authors.initials: Y
authors.lastname: Shinar
authors.forename: Marina
authors.initials: M
authors.lastname: Goldberg
authors.forename: Ilan
authors.initials: I
authors.lastname: Ben-Zvi
authors.forename: Pnina
authors.initials: P
authors.lastname: Langevitz
authors.forename: Avi
authors.initials: A
authors.lastname: Livneh
mesh_terms: D000369:Aged, 80 and over; D001145:Arrhythmias, Cardiac / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D010505:Familial Mediterranean Fever / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics; D007557:Israel; D007585:Jews / Q000235:genetics; D008136:Longevity / Q000235:genetics; D008297:Male; D009154:Mutation; D015995:Prevalence; D000071198:Pyrin
chemical_list: D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin