title: FNDC5 (irisin) gene and exceptional longevity: a functional replication study with rs16835198 and rs726344 SNPs.
abstract: Irisin might play an important role in reducing the risk of obesity, insulin resistance, or several related diseases, and high irisin levels may contribute to successful aging. Thus, the irisin precursor (FNDC5) gene is a candidate to influence exceptional longevity (EL), i.e., being a centenarian. It has been recently shown that two single-nucleotide polymorphisms (SNPs) in the FNDC5 gene, rs16835198 and rs726344, are associated with in vivo insulin sensitivity in adults. We determined luciferase gene reporter activity in the two above-mentioned SNPs and studied genotype distributions among centenarians (n = 175, 144 women) and healthy controls (n = 347, 142 women) from Spain. We also studied an Italian [79 healthy centenarians (40 women) and 316 healthy controls (156 women)] and a Japanese cohort [742 centenarians (623 women) and 499 healthy controls (356 women)]. The rs726344 SNP had functional significance, as shown by differences in luciferase activity between the constructs of this SNP (all P ≤ 0.05), with the variant A-allele having higher luciferase activity compared with the G-allele (P = 0.04). For the rs16835198 SNP, the variant T-allele tended to show higher luciferase activity compared with the G-allele (P = 0.07). However, we found no differences between genotype/allele frequencies of the two SNPs in centenarians versus controls in any cohort, and no significant association (using logistic regression adjusted by sex) between the two SNPs and EL. Further research is needed with different cohorts as well as with additional variants in the FNDC5 gene or in other genes involved in irisin signaling.
authors.affiliation: Department of Physiology, University of Valencia and Fundación para la Investigación del Hospital Clínico Universitario (INCLIVA), Av. Blasco Ibañez, 15, Valencia, 46010, Spain, fabian.sanchis@uv.es.
authors.forename: Fabian
authors.initials: F
authors.lastname: Sanchis-Gomar
authors.forename: Nuria
authors.initials: N
authors.lastname: Garatachea
authors.forename: Zi-hong
authors.initials: ZH
authors.lastname: He
authors.forename: Helios
authors.initials: H
authors.lastname: Pareja-Galeano
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Fuku
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.forename: Yasumichi
authors.initials: Y
authors.lastname: Arai
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Abe
authors.forename: Haruka
authors.initials: H
authors.lastname: Murakami
authors.forename: Motohiko
authors.initials: M
authors.lastname: Miyachi
authors.forename: Thomas
authors.initials: T
authors.lastname: Yvert
authors.forename: Catalina
authors.initials: C
authors.lastname: Santiago
authors.forename: Letizia
authors.initials: L
authors.lastname: Venturini
authors.forename: Carmen
authors.initials: C
authors.lastname: Fiuza-Luces
authors.forename: Alejandro
authors.initials: A
authors.lastname: Santos-Lozano
authors.forename: Gabriel
authors.initials: G
authors.lastname: Rodríguez-Romo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ricevuti
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Hirose
authors.forename: Enzo
authors.initials: E
authors.lastname: Emanuele
authors.forename: Alejandro
authors.initials: A
authors.lastname: Lucia
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D005353:Fibronectins / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007558:Italy; D007564:Japan; D016015:Logistic Models; D008136:Longevity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D013030:Spain; D055815:Young Adult
chemical_list: C577593:FNDC5 protein, human; D005353:Fibronectins