Assessment of age-related changes in heritability and IGF-1 gene effect on circulating IGF-1 levels.
It is well established that insulin-like growth factor 1 (IGF-1) circulating levels correlate with age and that heritability and influence of IGF-1 gene variation on IGF-1 levels also well-known. However, the influence of age on the genetic factors determining IGF-1 levels is not clear. In this study, we compared heritability estimates between younger (<52 years) and older (>52 years) twins and tested: (a) whether single nucleotide polymorphisms (SNPs) lying within 100 kbp of the IGF-1 gene are also associated with IGF-1 variation and (b) whether associated SNPs show interaction with age on IGF-1 levels. To achieve these aims, we measured plasma levels of IGF-1 and genotyped 18 SNPs with minor allele frequency >0.1 in a large sample, 4,471 UK female twins. Heritability explained 42 % of IGF-1 variation adjusted for age and in unadjusted sample was independent of age. Ten SNPs in four haploblocks showed significant association with IGF-1 levels, with p = 0.01-0.0005. The most distal SNP was located up to 90 kbp from the IGF-1 gene. When their age-dependent effects were examined, one SNP, rs855203, showed significant (p = 0.0009) age-dependent interaction effect on IGF-1 levels variation. This is the first study to test the age × genotype interaction in IGF-1 levels. The genomic region marked by rs855203 may consequently be of significance for further molecular and pharmacogenetic research, in particular in advanced age.
Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Liran
L
Franco
Frances M K
FM
Williams
Svetlana
S
Trofimov
Ida
I
Malkin
Gabriela
G
Surdulescu
Timothy
T
Spector
Gregory
G
Livshits
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D064368:Healthy Volunteers; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014427:Twins / Q000235:genetics*; D055815:Young Adult
D007334:Insulin-Like Growth Factor I; D004247:DNA