Table IV. Frequencies of ADIPOQ and LEP alleles and genotypes in control and elderly women subjects.

Genotypes Control Elderly and alleles group, n (%) group, n (%) p value rs2241766 ADIPQO* TT 28 (57.1) 29 (69.0) TG 16 (32.7) 12 (28.6) 0.266{ GG 5 (10.2) 1 (2.4) Allele T 72 (73.5) 70 (83.3) 0.115{ Allele G 26 (26.5) 14 (16.7) rs1501299 ADIPQO* GG 28 (57.1) 21 (50.0) GT 14 (28.6) 26 (31.0) 0.788{ TT 7 (14.3) 5 (11.9) Allele G 70 (71.4) 58 (69.0) 0.621{ Allele T 28 (28.6) 26 (31.0) rs266729 ADIPQO* CC 21 (42.9) 25 (59.5) CG 24 (49.0) 12 (28.5) 0.145{ GG 4 (8.1) 5 (12.0) Allele C 66 (67.3) 62 (73.8) 0.430{ Allele G 32 (32.7) 22 (26.2) rs7799039 LEP* AA 13 (26.5) 11 (26.2) AC 24 (48.9) 21 (50.0) 0.962{ CC 12 (24.4) 10 (23.8) Allele A 50 (51.0) 43 (51.2) 0.990{ Allele C 48 (49.0) 41 (48.8)

Several studies indicated that gender was a main variable in the genetics of longevity and suggested that men and women might follow different pathways to reach longevity [22–25]. Therefore, the effect of ADIPOQ and LEP genes SNPs on longevity were re- evaluated separately in each gender. Genotype frequency and allele frequency for rs1501299 ADIPOQ SNP and rs7799039 LEP gene promoter SNP were significantly different between the elderly and the young groups in men (genotype frequencies: p ¼ 0.011 for rs1501299 SNP and p ¼ 0.021 for rs7799039 SNP; alleles frequencies: p ¼ 0.011 for rs1501299 SNP and p ¼ 0.011 for rs7799039 SNP, Table III) but not in women (p ¼ 0.788 for rs1501299 SNP and p ¼ 0.962 for rs7799039 SNP, alleles frequencies: p ¼ 0.621 for rs1501299 SNP and p ¼ 0.990 for rs7799039 SNP, Table IV). On the

*All groups were in Hardy–Weinberg equilibrium (p40.05). {Fisher Exact test. {Chi Square test.

other hand, no significant difference was detected between the elderly and young control groups when gender was considered in the rs2241766 and rs266729 SNPs of ADIPOQ gene (for both SNPs, men: p 4 0.05, Table III, and women: p 4 0.05, Table IV).

variations in hormonal signalling pathways, body metabolism, immunity response, oxidative damage tolerance might account for such differences [38].

Results of this study showed absence of association between rs2241766 and rs266729 SNPs of ADIPOQ gene and longevity in both genders. Previous studies are variable concerning the association of rs2241766 or rs266729 SNP in ADIPOQ gene with age- associated diseases. Positive association of rs2241766 SNP has been reported in Korean population with coronary artery disease [39], and in Iranian population with type-2 diabetes [40]. In contrast, negative association with disease has been reported in Polish population with type-2 dia- betes, and Italian population with coronary artery diseases [31,32]. For – rs266729 SNP, positive association was reported in Spanish subjects with metabolic syndrome [8], while no association was detected between rs266729 SNP and survival among Ashkenazi Jewish population [17]. Therefore, ADI- POQ polymorphisms/age-related diseases associa- tions might have a population specific component. In addition, it is possible that Jordanians have different polymorphisms in the ADIPOQ gene that might buffer out or modulate the effect of the rs2241766 and rs266729 SNPs.

Discussion

Adiponectin and leptin are adipocyte-derived protein hormones that play a pivotal role in regulation of immune response and body metabolism [1]. Changes in plasma level/activity of adiponectin and leptin in adipocytes contribute to several age- associated diseases in human such as metabolic syndrome, coronary artery disease, hypertension, type-2 diabetes and cancer [4–7,13,16,26,27].

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Recently, a Japanese study showed that plasma adiponectin levels were significantly higher in elderly subjects from a longevity district compared to subjects from a non-longevity district [28] suggesting a possible role of adipokines in the pathway to human longevity. In this study, the possible association of three polymorphisms in ADIPOQ gene and one polymorphism in LEP gene with longevity phenotype was examined. Results showed that rs1501299 ADIPOQ SNP and rs7799039 LEP gene promoter SNP are associated with longevity in men but not in women. Previous studies have shown that the rs1501299 SNP is associated with low serum adiponectin [29,30], and increased susceptibility to coronary artery disease [26,30,31] and type-2 dia- betes [32]. Similarly, the rs7799039 LEP SNP is associated with transcriptional activity. It is located proximal to a binding site for the Sp1 transcription factor in the promoter region, and high expression occurs in the presence of CC genotype [11,12,33]. The clinical significance of this polymorphism has been demonstrated by its association with age-related diseases including cancer [13–15]. The finding that rs1501299 ADIPOQ and rs7799039 leptin SNPs play a role in human longevity provides more evidence of the clinical importance of these SNPs in age-related diseases.

Jordan is a small country located in Southwest Asia. The population is predominantly Arab (98%) [20] originally from Jordan and Palestine with approximately equal percentages. Since Jordanian and Palestinian share common ancestry, stratification due to migration of Palestinians to Jordan in 1948 is not expected to affect the results. In addition, the subjects (elderly and young) were recruited from different parts of Jordan without taking into con- sideration their origin and therefore, the sample is homogeneous.