Effects of Leptin Receptor Gene 3'-untranslated Region Polymorphism on Metabolic Profiles in Young Japanese Men

Abstract

We investigated the effects of leptin receptor gene 3'-untranslated region (3'-UTR) polymorphism on clinical and metabolic parameters in 221 young Japanese men aged 21 to 28 years. The polymerase chain reaction-restriction fragment length polymorphism method was used to identify a pentanucleotide (CTTTA) insertion in 3'-UTR of the leptin receptor gene. Body mass index, blood pressure, plasma glucose, insulin, leptin, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, free fatty acids, uric acid, apolipoprotein A-I (apoA-I), and cholesteryl-ester transfer protein levels were measured. There was only 1 homozygote and 38 heterozygotes for the 3'-UTR insertion allele among the 221 subjects. The insertion allele frequency was 0.090. Plasma HDL-cholesterol and apoA-I levels were significantly lower (p = 0.015 and p = 0.032 by Mann-Whitney U test, respectively) in homozygous or heterozygous carriers of the insertion allele than in subjects homozygous for the normal allele. There were no differences in other parameters measured. Furthermore, when the subjects were divided into three groups according to HDL-cholesterol level, the percentage of insertion allele-positive subjects was significantly lower in the highest HDL-cholesterol group (χ 2 = 8.42, p = 0.015). These findings suggest that serum HDL-cholesterol and apoA-I levels are influenced by the leptin receptor gene 3'-UTR polymorphism in young Japanese men. J Atheroscler Thromb, 2004; 11: 73-78.

Impact of leptin and leptin‐receptor gene polymorphisms on serum lipids in Japanese obese children

“…Nishikai et al. reported that, in non‐diabetic adults, HDL‐C levels and apolipoprotein A‐I levels were influenced by LEPR gene 3′‐untranslated region polymorphism (14). Takahashi‐Yasuno et al.…”

“…Many epidemiological and clinical studies have been performed to investigate the association between leptin/LEPR gene polymorphisms and obesity, demonstrating the limited influence of the gene polymorphisms (10,11). In Japanese, the effect of leptin gene polymorphisms on obesity is controversial (12,13), and no association was found between LEPR gene polymorphisms and obesity (14–18). Several studies in humans, however, demonstrated that some LEPR gene polymorphisms had significant influences on complications of obesity, such as hypertension (19), glucose intolerance (17) or sleep apnea syndrome (20).…”

Genetic variation in leptin receptor gene is associated with type 2 diabetes and body weight: The Finnish Diabetes Prevention Study

“…7,8 None of the earlier studies on this 3 0 UTR variation have shown any association with body weight, as we demonstrated in the present study. However, none of them included IGT subjects, but morbidly obese subjects, 6,7 young healthy men 9 or a population-based cohort. 8 To our knowledge there is only one previous association study on LEPR variants in IGT population, 12 but it did not cover the Del/Ins polymorphism.…”

“…The Del/Ins polymorphism has been found to be associated with serum insulin levels, [6][7][8] serum HDL-cholesterol and ApoA-I levels 9 and susceptibility to type 2 diabetes. 8 Lakka et al 8 showed…”

CTTTA Deletion/Insertion polymorphism in 3'-UTR of LEPR gene in type 2 diabetes subjects belonging to Kashmiri population

“…The genotype and allele frequency of this polymorphism in our population is comparable to another study in which the carriers of the insertion allele had a 79% reduced risk of T2DM compared with non-carriers in the 4-year follow-up [ 19 ]. The Del/Ins variant has been found to be associated with serum insulin levels [ 17 , 19 ], serum high density lipoprotein (HDL)-cholesterol and apolipoprotein A (apo A)-I levels [ 20 ], and susceptibility to T2DM [ 20 – 22 ]. In our study the intra group genotyping among both cases and controls explicated a positive correlation between the Del allele and the imperative risk factors that predispose our population to T2DM.…”