Chromosome 1p13, which encodes lymphoid protein tyrosine phosphatase (LYP), plays a crucial role in the negative control of T lymphocyte activation. LYP is expressed in lymphoid cells, mainly in T lymphocytes, where it associates with C-terminal Src kinase (CSK) to form a complex that suppresses the T-cell receptor signaling kinases LCK and FYN [12, 13]. Recently, a variant of PTPN22 (rs2476601, 1858C>T) has been associated with an increased risk for the development of multiple autoimmune diseases including type 1 diabetes (T1D) [14-16], rheumatoid arthritis [17], systemic lupus erythematosus [18], and Graves' disease [19]. This variant is a single nucleotide change at residue 1858 from C to T, which results in a single amino acid substitution from arginine to tryptophan at position 620 of the Lyp protein (Lyp 620W). Experimental evidence suggests that the disease-associated LYP variant Trp620 prevents the interaction of LYP with CSK [14]. Consequently, the T-cell receptor-associated kinases mightThe maximum age of males and females in our sample population was 100 and 106, respectively. Only one subject carrying the PTPN22 T*/T* genotype was found. Allelic and genotypic frequencies were in Hardy-Weinberg equilibrium, regardless of whether males and females were considered together (χ² = 0.15, P = 0.698) or separately (males: χ² = 0.56, P = 0.454; females: χ² = 0.15, P = 0.698). The same situation occurred when age groups were considered (Table 1). For both genders, the frequency of PTPN22*T carriers did not differ significantly in nona/centenarians and in octogenarians with respect to the young group (Table 1). Overall, there was a trend toward higher frequencies of PTPN22*T carriers among females (10.2 vs. 7.2%, P = 0.08), but the frequency of *T carriers was not significantly associated with gender in each age group studied. Allele frequencies did not differ significantly among age groups (females χ² = 0.57, P = 0.752; males χ² = 0.33, P = 0.8479). The three-way contingency table analysis by log-linear model confirmed the irrelevant effect of PTPN22 genotype on the determination of life-span expectancy in the population x=age group; y=PTPN22 genotype (PTPN22 C*/C* PTPN22*T carriers); z=sex significant differences were reported (Table 3). We also carried out a comparison between the genotype frequencies of octogenarians-nona/centenarians and the pooled genotype frequency of younger individuals; no significant result was found (octogenarians, OR for T* carriers = 1.037, 95% CI 0.693-1.551, P = 0.862; nona/centenarians, OR for T* carriers = 1.253, 95% CI 0.800-2.014, P = 0.351), further confirming the results obtained from our study population. Of note, this comparison had sufficient power (0.80) to detect an association with a genotypic relative risk (or odds ratio) below 0.80 and/or above 1.2, thus excluding a marginal effect of PTPN22 1858C[T SNP on human longevity.

Discussion
Ageing is characterized by a pro-inflammatory status that could contribute to the onset of major age-related diseases. Indeed, genetic variations in pro- or anti-inflammatory cytokines were found to influence successful ageing and longevity [24]. These polymorphisms might confer flexibility in the immune response by allowing differential production of cytokines. Cytokine gene polymorphisms have been shown to be involved in the susceptibility, severity and clinical outcome of several diseases [25]. In particular, high producer alleles of pro-inflammatory cytokines have been associated with inflammatory age-related diseases [26] and disability [27] and with a decreased probability to reach extreme longevity [28]. Consequently, it can be hypothesized that anti-inflammatory cytokines might be involved in successful ageing and longevity.

As the PTPN22 gene product LYP is an important down-regulator of T lymphocyte activation and PTPN22-knockout mice showed selective dysregulation in the effector/memory T-cell compartment, with hyper-proliferation and early signaling responses in re-stimulated T cells [29], we wanted to test whether the PTPN22 1858C[T (R620W) polymorphism was associated with longevity.

To further support our results, allele and genotype frequencies of the younger group were compared with those reported in previously published studies carried out on control individuals with Italic ancestry (age <70 years), comprising the re-analysis of our previous data [23]. No significant differences were found.