Association of a near-MC4R gene variant (rs17782313) with hyperphagia among patients with severe obesity

Obesity is a multifaceted issue influenced by genetic, environmental, and psychological factors. Genetic predispositions significantly contribute to the risk of obesity in individuals. A deficiency in the melanocortin-4 receptor (MC4R) gene is recognized as the most prevalent single-gene cause of obesity and also plays a significant role in polygenic obesity. This study aimed to assess the association between the MC4R rs17782313 variant and hyperphagia in Iranian patients with obesity.

Genotypes of the near-MC4R variant rs17782313 were compared between patients with severe obesity and hyperphagia (cases) and patients with severe obesity without hyperphagia (controls). Factors such as body mass index (BMI), family history of obesity before puberty, and age at onset of obesity were also assessed. The genotyping of the MC4R rs17782313 variant was conducted using the RFLP-PCR method.

Analysis of the variant rs17782313 demonstrated a statistically significant positive association with hyperphagia among patients with obesity (ꭓ²: 6.29, df: 2; p = 0.043). Among those who reported hyperphagia, 36.5% exhibited the TT genotype, while 50% had the TC genotype and 13.5% had the CC genotype. In the dominant model (TC + TT vs. CC), the combined presence of TC and TT genotypes was found in 86.5% of patients with obesity and hyperphagia compared to 13.5% of patients who had the CC genotype, suggesting an increased likelihood of hyperphagia (p = 0.028; OR = 3.2, 95% CI: 1.13-8.91) according to a cross-tabulation association test. Also, the cross-tabulation analysis under the additive model (CC = 0, TC = 1, TT = 2) showed a significant association of the heterozygote genotype (TC vs. CC) with susceptibility to hyperphagia among patients with obesity (p = 0.017; OR = 3.99, 95% CI: 1.27-13.09). Logistic regression analysis also confirmed the results even after adjustment for age under the dominant model (TC + TT vs. CC; p = 0.024; OR (95% CI) = 3.2 (1.16-8.92)).

These findings underscore the importance of genetic factors in understanding hyperphagic behaviors. The MC4R rs17782313 variant is significantly associated with hyperphagia among patients with obesity in the Iranian population.