Leptin and the GA genotype of rs2167270 of the LEP gene increase the risk of prediabetes.

Prediabetes is a precursor stage that frequently develops to definitive type 2 diabetes mellitus (T2DM). Therefore, identifying individuals with prediabetes can allow for early intervention measures that delay or prevent disease progression to T2DM. Several biochemical changes appear to be associated with prediabetes, including an increase in the serum levels of leptin. In Jordan, this association has not been previously investigated. In the present study, the serum levels of leptin were measured in 122 prediabetes subjects and 122 controls. Furthermore, the genotypes of three single nucleotide polymorphisms in the LEP gene (rs7799039, rs2167270 and rs791620) were investigated for their association with prediabetes using PCR-restriction fragment length polymorphism. The results revealed a significant increase in serum leptin levels in the prediabetes group. It was also shown that the GA genotype and the A allele of rs2167270 were significantly associated with an increased risk of prediabetes (P<0.05). These findings were shown to be independent of body mass index, waist circumference and serum glucose levels. To the best of our knowledge, the present study is the first in Jordan to have reported an association between serum leptin levels and the GA genotype of rs2167270 with an increased risk of prediabetes, identified both in the univariate and multivariate models.

Sildenafil reverses the hypertrophy of mice right ventricle caused by hypoxia but does not reverse the changes in the myosin heavy chain isoforms.

In this study, we investigated the effect of hypoxia and concomitant sildenafil treatment on MHC isoforms in hypoxia-induced hypertrophied right ventricles. Right ventricular hypertrophy was induced in mice by exposing them to hypoxic stimulus (11% ambient oxygen) in a normobaric chamber for 20 days. 45 mice were used in this study, distributed randomly into three groups: the first group served as a control (CO), the second group was exposed to hypoxia for 20 days without sildenafil treatment (HY), and the third group was given sildenafil orally at a dose of 30 mg.kg-1.day-1 plus exposure to hypoxia for 20 days (HS). Relative amounts of MHC isoforms were calculated using two ELISA kits containing antibodies against α and ß MHC, and by SDS-PAGE. Compared with the CO group, the HY group showed a significant increase in right ventricle weight/left ventricle plus septum ratio (Fulton's ratio). The HS group showed a significant decrease in Fulton's ratio compared with the HY group, but not with the CO group. Expression of the MHC-ß isoform was significantly increased in the HY group compared with the CO group. There was no significant difference in MHC-ß between the HY group and the HS group. Plasma atrial natriuretic peptide level was significantly higher in HY group than HS group and did not return to normal after sildenafil treatment. Conclusion: sildenafil reversed the right ventricular hypertrophy induced by hypoxia but did not decrease the expression of MHC-ß to normal levels.