Association between Age and the 7 Repeat Allele of the Dopamine D4 Receptor Gene

Abstract

Longevity is in part (25%) inherited, and genetic studies aim to uncover allelic variants that play an important role in prolonging life span. Results to date confirm only a few gene variants associated with longevity, while others show inconsistent results. However, GWAS studies concentrate on single nucleotide polymorphisms, and there are only a handful of studies investigating variable number of tandem repeat variations related to longevity. Recently, Grady and colleagues (2013) reported a remarkable (66%) accumulation of those carrying the 7 repeat allele of the dopamine D4 receptor gene in a large population of 90–109 years old Californian centenarians, as compared to an ancestry-matched young population. In the present study we demonstrate the same association using continuous age groups in an 18–97 years old Caucasian sample (N = 1801, p = 0.007). We found a continuous pattern of increase from 18–75, however frequency of allele 7 carriers decreased in our oldest age groups. Possible role of gene-environment interaction effects driven by historical events are discussed. In accordance with previous findings, we observed association preferentially in females (p = 0.003). Our results underlie the importance of investigating non-disease related genetic variants as inherited components of longevity, and confirm, that the 7-repeat allele of the dopamine D4 receptor gene is a longevity enabling genetic factor, accumulating in the elderly female population.

The VNTR 48 bp Polymorphism in the DRD4 Gene Is Associated with Higher Tobacco Smoking in Male Mexican Mestizo Smokers with and without COPD

“…The results of the genetic analysis demonstrated no association between the presence of the 7 repeat allele in the DRD4 gene and higher cigarette consumption, or among those patients with a diagnosis of COPD secondary to smoking where nicotine addiction (evaluated by Fagerström test) was higher. The frequencies of the short (S) and long (L) alleles in the study population were similar to the rest of the populations previously reported in the literature [10,[22][23][24][25].…”

G protein-coupled receptors that influence lifespan of human and animal models

“…A negative association was also observed between human longevity and the presence of the minor variant G of the SNP rs6276, mainly when the allele is homozygous, and this is explained because said SNP causes the DRD2 mRNA to degrade more rapidly when enhance its binding to various miRNAs such as miR-485-5p (Crocco et al 2016 ). Meanwhile, a variable number tandem repeat (VNTR) has been reported in the third exon of the DRD4 gene and the seven-repeat allele was associated with increased levels of physical activity and longevity, preferably in women (Grady et al 2013 ; Szekely et al 2016 ).…”