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

Abstract

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.

Functionally Significant Variants in Genes Associated with Abdominal Obesity: A Review

“…In a study on common variants in the leptin gene, researchers showed an association of the AA genotype of the rs7799039 variant with the development of obesity in the population of South India [ 136 ]. The A allele of rs2167270 significantly correlates with an elevated risk of prediabetes in Jordan and in the population of South India [ 137 , 138 , 139 ]. Rs6966536 (allele G) of the LEP gene has been implicated in the development of obesity in a South African population [ 140 ].…”

The Association of Leptin Gene Polymorphisms with Crohn's Disease in a Chinese Pediatric Population

“…Instead, the A allele and GG genotype of rs2167270 were more prevalent among atopic dermatitis patients (13). Aljanabi et al (19) also showed that both the A allele and GA genotype of rs2167270 of the leptin gene are highly associated with the prevalence of prediabetes (P < 0.05). The different genotypes of SNP rs2167270 are thought to be associated with higher or lower expression of the LEP gene (20).…”

Leptin and the rs2167270 Polymorphism Are Associated with Glycemic Control in Type Two Diabetes Mellitus Patients on Metformin Therapy

“…It was also found that patients with poor glycemic control have lower serum leptin levels. Interestingly, our group showed that Jordanian patients who have prediabetes, a state characterized by elevated levels of serum leptin, are more likely to carry the GA genotype of rs2167270 [ 21 ]. Taken together, it could be hypothesized that in Jordan, the GA genotype of rs2167270 is linked with metabolic conditions associated with elevated levels of serum leptin.…”

“…Leptin is a hormone-like adipokine secreted by adipose tissue cells [ 21 , 22 ]. Inactivating mutations in the gene that codes for the leptin hormone ( LEP ) are linked with obesity in humans [ 23 ] and in rodent models [ 24 ].…”