As far as cytokine production is concerned, the ) ) 1082 G⁄A IL-10 promoter SNP and the 308 G⁄A TNF-a promoter SNP considered are functionally important. Low production of IL-10 occurs in the presence of 1082 A allele (Turner et al., 1997; Cacev et al., 2008) while high production of TNF-a occurs ) in the presence of 308A allele (Makhatadze, 1998). Thus, the experimental and control groups were divided into four categories based on the expression levels of TNF-a and IL-10 as shown in Table 2 to examine the cytokine gene polymorphisms in combina- tion (i.e. certain haplotypes could account for one part of the genetic component of longevity). Still, no differ- ence in the distribution of the ‘functional’ genotypes between the elderly and control subjects (Fisher’s exact, P > 0.05).

Discussion

Interleukin 10 and TNF-a are cytokines, which have primarily opposing roles in the inflammatory reaction. IL-10 is an anti-inflammatory cytokine whereas TNF-a is a pro-inflammatory cytokine (Makhatadze, 1998; Moore et al., 2001; Koh et al., 2008). Differences in the regulation of IL-10 and TNF-a production may be critical with respect to the final outcome of an inflam- matory response. Production of these cytokines is ) largely controlled by 1082 G⁄A promoter SNP and ) 308 G⁄A promoter SNPs respectively (Turner et al., 1997; Cacev et al., 2008; Turner et al., 1997;

Additionally, some reports have shown that IL-10 ) 1082 G⁄A modulates longevity differently in men and women (Lio et al., 2002a, 2003). Therefore, the

Table 1. Frequencies of IL-10 and TNF-a alleles and genotypes in elderly and control groups

Table 3. Frequencies of IL-10 and TNF-a alleles and genotypes in elderly and control men subjects

Genotypes Control group Elderly group and alleles N (%) N (%) P-value )1082 IL-10a AA 50 (42.5) 60 (50.4) AG 61 (51.7) 55 (46.2) 0.384 GG 7 (5.9) 4 (3.4) 0.225 Allele A 161 (68.2) 175 (73.5) Allele G 75 (31.8) 63 (26.5) )308 TNF-aa AA 3 (2.5) 2 (1.7) AG 18 (15.3) 21 (17.6) 0.828 GG 97 (82.2) 96 (80.7) 1.000 Allele A 24 (10.2) 25 (10.5) Allele G 212 (89.8) 213 (89.5)

Control Elderly Genotypes men group men group and alleles N (%) N (%) P-value )1082 IL-10 AA 26 (36.1) 43 (55.1) AG 41 (56.9) 33 (42.3) GG 5 (6.9) 2 (2.6) 0.045 Allele A 93 (64.6) 119 (76.3) Allele G 51 (35.4) 37 (23.7) 0.031 )308 TNF-a AA 0 (0) 1 (1.3) AG 12 (16.7) 13 (16.7) GG 60 (83.3) 64 (82.1) 1.00 Allele A 12 (8.3) 15 (9.6) Allele G 132 (91.7) 141 (90.4) 0.840

aAll groups were in Hardy–Weinberg equilibrium (P > 0.05).

tion (Wang et al., 2001) and in the Sardinian popula- tion (Pes et al., 2004). Thus, cytokine⁄longevity associations might have a population specific compo- nent, being affected by the population specific gene pool as well as by gene-environment interaction. In this study, we examined the effect of these polymor- phisms on the genetic components of longevity in the Jordanian population.

Table 4. Frequencies of IL-10 and TNF-a alleles and genotypes in elderly and control women subjects

Control Elderly Genotypes women group women group and alleles N (%) N (%) P-value )1082 IL-10 AA 24 (52.2) 17 (41.5) AG 20 (43.5) 22 (53.7) GG 2 (4.3) 2 (4.9) 0.617 Allele A 68 (73.9) 56 (68.3) Allele G 24 (26.1) 26 (31.7) 0.502 )308 TNF-a AA 3 (6.5) 1 (2.4) AG 6 (13) 8 (19.5) GG 37 (80.4) 32 (78) 0.587 Allele A 12 (13) 10 (12) Allele G 80 (87) 72 (87.8) 1.000

The average age of the current study participants (i.e. 90.2 years) is usually considered oldest old. In Jordan, the mortality rate starts inclining exponentially at 50 years old reaching maximum level in the seven- ties indicating reaching above 85 years old is a rarity (Khoury et al., 1999). Therefore, oldest old people are considered exceptional individuals in Jordan as cente- narians in the Western populations with higher life expectancies.

One of the limitations of this study was the lack of data regarding plasma levels of IL-10 and TNF-a, but the functional relevance of the polymorphisms studied is well documented, as presented in the above discus- sion. In addition, other polymorphisms might be pres- ent in the promoter region of these cytokines in the Jordanian population that potentially modulate the effect of the studied polymorphisms. Therefore, screen- ing for the presence of these modifier polymorphisms in addition to direct measurements of the plasma level IL-10 and TNF-a is warranted in future studies.

Makhatadze, 1998; Cacev et al., 2008). In this study, we asked whether or not these cytokine gene polymor- phisms could account for one part of the genetic com- ponent of longevity in Jordanian population.