In this study, IL-6 and MT2A polymorphisms in a sample of 354 healthy Turkish subjects were compared according to their ages, age groups, and genders. The genotype frequencies of IL-6 (cid:2)174 G/C and MT2A (cid:2)5 A/G polymorphisms in all samples were consistent with Hardy-Weinberg equilibrium. Volunteers were subdivided into four groups according to their ages as 2040 years, 4160 years, 6180 years, and >80 years. Genotype frequencies of IL-6 and MT2A polymorphisms in male and female subjects were compared with the x2-test, and no significant difference was found between the two genders.

The genotype frequencies of the IL-6 (cid:2)174 G/C promoter region SNP were determined to be as follows: 44.6% homozygote typical (GG), 46.9% heterozygote (GC), and 8.5% homozygote atypical genotype (CC). The mean ages of individuals with homozygote typical, heterozygote, and homozygote atypical genotype were 49.82 ± 20.45 years, 58.57 ± 17.02 years, and 66.73 ± 14.00 years, respectively. A highly statistically significant association was detected between IL-6 genotype and allele frequencies in aging.

In addition, the frequency of the IL-6 (cid:2)174 C+ carriers in the age groups of 4160 years, 6180 years, and >80 years was higher than that in the age group of 2040 years.

There was a significant association between (cid:2)174 G/C promoter region polymorphism and MT2A (cid:2)5 A/G promoter region polymorphism with longevity in Turkish individuals. IL-6 is a key proinflammatory cytokine and (cid:2)174 G/C SNP polymorphism located within the promoter regions of IL-6 gene, determining increased or decreased production of inflammatory cytokines has been reported. Results of case-control and prospective studies in associations with the IL-6 (cid:2)174 G/C promoter region polymorphism and successful aging have been very conflicting. 

This study was partly supported by The Scientific and Technical Council of Turkey (TUBITAK; Project No: 109S248, 2010).In an Italian elderly population (The Treviso Longeva-Trelong study), an increase in interleukin-6 plasma levels with age was observed, with a sex-specific contribution of rs1800795 polymorphism (Albani et al., 2009). Nevertheless, several studies have reported a positive association between the IL-6 (cid:2)174 G/C polymorphism and longevity, and the ability to produce low levels of IL-6 throughout the lifespan seems to be beneficial for longevity (Bonafe` et al., 2001; Christiansen et al., 2004; Franceschi et al., 2005). MT gene expression is induced by pro-inflammatory cytokines during stress and inflammation. The interrelationships among inflammatory cytokines, stress, MT expression level, and zinc ion bioavailability are crucial to achieving healthy longevity (Mocchegiani and Malavolta, 2008). The analysis of some polymorphisms in MT genes confirms this assumption. The studies performed so far regarding the relationship between several MT polymorphisms and aging and age-related disease have usually been conducted in the Italian population by the same research group. Recent findings have shown that MT1A +647 A/C coding region polymorphism affects the inflammatory status, and this polymorphism is associated with longevity in the Italian population (Cipriano et al., 2006). Also, MT1A +647 C+ carriers displayed higher IL-6 levels, and they were more likely to develop type 2 diabetes and cardiovascular complications. However, in the same study, concerning +1245 A/G MT1A polymorphism, no differences in genotypic and allelic distribution were found among healthy old control groups (Giacconi et al., 2008). In another polymorphism at the untranslated region of MT2A (+838 C/G), it is observed that elderly subjects carrying C(cid:2) allele had a higher risk of developing carotid artery stenosis (Giacconi et al., 2007). Giacconi et al. (2008) reported a significant relationship between MT2A (cid:2)209 A/G promoter region polymorphism, diabetes type II, and atherosclerosis disease. Moreover, they found out that G(cid:2) carriers display higher circulating IL-6 levels compared to G+. Another polymorphism regarding MT2A is (cid:2)5 A/G SNP, and this polymorphism is located at the core promoter region of the MT2A gene where gene transcription initializes. There have been only a few studies on MT2A (cid:2)5 A/G SNP in the literature, and a significant association has been found between this polymorphism and Cd levels in autopsy renal tissues (Kayaalti et al., 2010), whereas no other association with longevity or age-related diseases was observed.disease. Pl. Med.

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