Polymorphisms in the adiponectin and leptin genes are important for regulating body metabolism and immune response. Many studies have shown that gene variants play a role in age-associated diseases. In this study, we investigated the contribution of rs266729, rs2241766 (45T/G), and rs1501299 (276 G/T) SNPs of the adiponectin gene (ADIPQO) and rs7799039 SNP of the leptin (LEP) gene to the human longevity phenotype in the Jordanian population. Polymorphisms were studied in 110 randomly selected elderly subjects (aged 85 years or older) with a mean age of 90.2 years and 120 young controls (aged 20 to 50 years) with a mean age of 32.0 years. No significant differences were detected in the genotype and allele frequencies of examined gene variants between the two groups (p > 0.05). However, when gender was considered, allele frequencies of rs1501299 SNP in ADIPOQ gene and rs7799039 in LEP gene were significantly associated with longevity in men (p < 0.02) but not in women (p > 0.05). Thus, ADIPOQ and LEP genes polymorphisms play a gender-specific role in the pathway to men's longevity.

Adiponectin and leptin are adipokines secreted from white adipose tissue that function like hormones to regulate body metabolism and immune responses. Adiponectin activates multiple signalling pathways that mediate its anti-diabetic, anti-atherogenic, and anti-inflammatory functions; therefore, adiponectin plays a protective role against age-related diseases. Low levels of adiponectin have been implicated in several late-onset disease states such as insulin resistance and type-2 diabetes, cardiovascular disease, hypertension, and dyslipidemia. Several single nucleotide polymorphisms (SNPs) in the ADIPOQ gene that codes for adiponectin have been shown to affect levels or activity of adiponectin and have been associated with age-related diseases. For example, the promoter rs266729 SNP lowers the circulating levels of adiponectin and has a strong association with metabolic syndrome among Spanish and French populations. Furthermore, rs2241766 and rs1501299 SNPs in ADIPOQ gene, which alter adiponectin activity, are associated with metabolic phenotype.

Leptin, on the other hand, is significantly increased in individuals suffering from obesity, diabetes mellitus, hypertension or metabolic syndrome. A common promoter polymorphic site rs7799039 SNP in the leptin (LEP) gene is associated with transcriptional activity leading to reduced circulating leptin concentrations in subjects with AA genotype. This polymorphism is also associated with multiple age-related diseases in several populations such as breast cancer among Tunisians, and non-small cell lung cancer and prostate cancer among Portuguese.

Since adiponectin and leptin play an important role in body homeostasis and susceptibility to age-related diseases, allelic variants that change the levels and/or activity of adiponectin and leptin might be involved in the pathway of human longevity. Indeed, two allelic variants in ADIPOQ gene, rs17300539 (711391G/A) and 2019A/7, are associated with longevity in Ashkenazi Jewish population. In the current study, we investigated the contribution of rs266729, rs2241766, and rs1501299 SNPs in ADIPOQ gene and rs7799039 SNP in LEP gene to longevity phenotype in Jordanian population. Results showed that rs1501299 SNP in ADIPOQ gene and rs7799039 SNP in promoter region of LEP gene play a gender-specific role in human longevity.

Blood samples (13 ml) were obtained from all subjects, and DNA was extracted using the Wizard DNA Extraction Kit. The genotype distributions of the examined polymorphisms were analysed in agreement with Hardy-Weinberg equilibrium. Statistical evaluation of results was done by comparing allele, genotype and predicted phenotype distributions using the chi-square test. If n < 5, exact Fisher statistic was used. The SPSS 15.0 statistical software package (SPSS Inc., Chicago, IL) was used for all statistical evaluations. Because several significant associations were observed among the 24 associations examined in the study, which exceeds the number that might be observed by chance (one significant association/24 tests), a p-values of 0.05 was considered significant without adjustments for multiple comparisons.

In conclusion, the polymorphisms in ADIPOQ and LEP genes play a gender-specific role in human longevity and may be involved in the pathway of human longevity.Processed Text:

rs7799039 LEP* 

AA 16 (22.5) 23 (33.8) 
AC 29 (40.8) 34 (50.0) 
0.021{ 
CC 26 (36.6) 11 (16.2) 

Allele A 61 (43.0) 80 (58.8) 
0.011{ 
Allele C 81 (57.0) 56 (41.2) 


Genotypes Control Elderly p and Alleles group, n (%) group, n (%) value 

rs2241766 ADIPOQ* 

TT 68 (56.6) 70 (63.6) 
TG 43 (35.8) 37 (33.6) 
0.231{ 
GG 9 (7.6) 3 (2.8) 

Allele T 179 (74.6) 177 (80.5) 
0.164{ 
Allele G 61 (25.4) 43 (19.5) 


rs1501299 ADIPOQ* 

GG 49 (40.8) 58 (52.7) 
GT 56 (46.6) 43 (39.1) 
0.172{ 
TT 15 (12.6) 9 (8.2) 

Allele G 154 (64.2) 159 (72.3)
0.078{ 
Allele T 86 (35.8) 61 (27.7)


rs266729 ADIPOQ* 

CC 69 (57.5) 68 (61.8)
CG 43 (35.8) 35 (31.8)
0.809{ 
GG 8 (6.7) 7 (6.4) 

Allele C 181 (75.4) 171 (77.7)
0.635{ 
Allele G 59 (24.6) 49 (22.3)


rs7799039 LEP* 

AA 29 (24.2) 34 (30.9) 
AC 53 (44.2) 55 (50) 
0.082{ 
CC 38 (31.6) 21 (19.1)

Allele A 111 (46.3) 123 (55.9)
0.051{ 
Allele C 129 (53.7) 97 (44.1)


*All groups were in Hardy-Weinberg equilibrium (p<0.05). {Fisher Exact test. {Chi Square test.

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*