Human chitotriosidase polymorphism is associated with human longevity in Mediterranean nonagenarians and centenarians

Abstract

Human phagocyte-specific chitotriosidase (CHIT-1) is a chitinolytic enzyme associated with several diseases involving macrophage activation. Previous studies have demonstrated that a high activity of Chit could have widespread effects on atherosclerosis, cardiovascular disease and dementia. The 24-bp duplication in the CHIT-1 gene is associated with a deficiency in enzymatic activity. In this study, we attempted to assess whether CHIT-1 could be a plausible candidate gene responsible for human longevity. Therefore, we compared the distribution of the CHIT-1 polymorphism genotype in three different populations of the Mediterranean area (Italian, Greek and Tunisian) aged over 90 years. As a control group for each nonagenarian and centenarian, a 60-70-year-old subject was genotyped. We found that the heterozygote frequency for the 24-bp duplication in the CHIT-1 gene was not significantly different among the oldest old subjects of Mediterranean populations, whereas it was significantly different between oldest old subjects and control subjects, being highest among the oldest old subjects and lowest among control groups. In the oldest old group, no subject was observed to be homozygous for CHIT-1 deficiency. Moreover, the mean enzymatic activity in heterozygous oldest subjects was lower than that in the control group. These data indicate that the heterozygosis for a 24-bp duplication in the CHIT-1 gene could have a protective effect in human longevity.

Comparison of YKL-39 and CHIT-1 expression during macrophages differentiation and polarization

“…Numerous evidences report the central role of CHIT-1 in the expanding spectrum of disorders suggesting that overproduction of CHIT-1 could exert deleterious effect in many degenerative disorders [24]. This concept is also sustained by our previous findings in which we observed that genetic variation within the CHIT-1 gene was strongly associated with human longevity and with several phenotypes of healthy aging [39], and that a functional polymorphism in the CHIT-1 gene protects from NAFLD progression [40]. Alternative or "M 2 " macrophages, reproduce the Th2 response of T cells and are considered anti-inflammatory; they express an array of phagocytic receptors, anti-inflammatory cytokines and release products that promote tissue regeneration and healing.…”

Does 24bp Duplication of Human CHIT1 Gene (Chitotriosidase1) Predispose to Filarial Chyluria? A Case-Control Study

“…Several genes and their alteration contribute to disease susceptibility and outcomes especially in cases of autoimmune disorders and malignancies [7]. Investigators have tried to evaluate the role of genetic susceptibility to infectious disease also [8].…”

Dup-24 bp in the CHIT1 Gene in Six Mexican Amerindian Populations

“…Although the null clinical significance of the dup-24 bp polymorphism in the CHIT1 gene has been established for some time now (Boot et al 1998;Canudas et al 2001;Piras et al 2007), it has not been determined if there is a clinical significance of the high frequency of homozygosity of dup-24 bp in CHIT1 in Amerindian populations. Some authors have proposed that a CHIT deficiency can increase the susceptibility to infections due to parasites containing chitin (Malaguarnera et al 2003), but this implication has to be tested in a future study.…”

“…The biologic significance of the very high frequency of this gene polymorphism remains unexplained, which suggests it may have a selective advantage not yet completely understood (Canudas et al 2001;Lee et al 2007). In the African population, the dup-24 bp homozygous state is rare, with an estimated frequency of 2% (Malaguarnera et al 2003). In contrast, the frequency of the homozygous status is approximately 6% in Caucasians (Boot et al 1999).…”