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

Abstract

Background: Leptin is thought to play an important role in Crohn's disease (CD) pathogenesis and progression. Independent studies have revealed a strong upregulation of leptin expression in the mesenteric fat of CD patients. Objectives: This study assessed the relationship between leptin gene polymorphisms and CD susceptibility in a Chinese pediatric population. Methods: A total of 86 patients with CD and 142 healthy controls were recruited for this case-control study. The genotypes of 4 single-nucleotide polymorphisms (SNPs; rs2071045, rs41457646, rs11761556, and rs2167270) in the leptin gene were determined by multiplex polymerase chain reaction (PCR) combined with next-generation sequencing. Results: We found that leptin rs2167270 had a significantly different distribution of alleles and genotypes between CD patients and healthy controls (G is a risk allele: 83.7% of cases vs 72.5% of controls; odds ratio [OR] 1.947; 95% CI, 1.203-3.151; P = 0.006; GG is a risk genotype: 72.1% of cases vs 53.5% of controls; P = 0.021). Patients with the CC genotype (rs2071045) had a significantly increased risk of early onset of CD (58.3% in A1a vs 31.1% in A1b; P = 0.003). Similarly, patients carrying the G allele (100% in A1a vs 84.1% in A1b; P = 0.015) and GG genotype (100% in A1a vs 71.0% in A1b; P = 0.048) of rs41457646, A allele (93.3% in A1a vs 71.8% in A1b; P = 0.013) and AA genotype (93.3% in A1a vs 47.9% in A1b; P = 0.003) in rs11761556 had a higher risk of early onset of CD. However, there was no significant difference in any of these 4 SNPs between patients with and without perianal lesions, as well as in low and normal body mass index (BMI) patients. Conclusions: The leptin rs2167270 polymorphism is associated with the susceptibility to CD in a Chinese pediatric population. Leptin rs2071045, rs41457646, and rs11761556 might lead to the early onset of pediatric CD.