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- Title
MC4R Variant rs17782313 Associates With Increased Levels of DNAJC27, Ghrelin, and Visfatin and Correlates With Obesity and Hypertension in a Kuwaiti Cohort.
- Authors
Hammad, Maha M.; Abu-Farha, Mohamed; Hebbar, Prashantha; Cherian, Preethi; Al Khairi, Irina; Melhem, Motasem; Alkayal, Fadi; Alsmadi, Osama; Thanaraj, Thangavel Alphonse; Al-Mulla, Fahd; Abubaker, Jehad
- Abstract
Melanocortin 4 receptor (MC4R), a notable component of the melanocortin system, regulates appetite, body weight, and energy homeostasis. Genome-wide association studies have identified several MC4R variants associated with adiposity; of these, rs17782313, which is associated with increased body mass index (BMI) and overeating behavior, is of particular interest. Another gene associated with increased adiposity in global genome-wide association studies is DNAJC27 , a heat shock protein known to be elevated in obesity. The detailed mechanisms underlying the role of MC4R variants in the biological pathways underlying metabolic disorders are not well-understood. To address this, we assessed variations of rs17782313 in a cohort of 282 Arab individuals from Kuwait, who are deeply phenotyped for anthropometric and metabolic traits and various biomarkers, including DNAJC27. Association tests showed that the rs17782313_C allele was associated with BMI and DNAJC27 levels. Increased levels of DNAJC27 reduced the MC4R-mediated formation of cAMP in MC4R ACTOne stable cells. In conclusion, this study demonstrated an association between the rs17782313 variant near MC4R and increased BMI and DNAJC27 levels and established a link between increased DNAJC27 levels and lower cAMP levels. We propose that regulation of MC4R activity by DNAJC27 enhances appetite through its effect on cAMP, thereby regulating obesity.
- Subjects
KUWAIT; HEAT shock proteins; GHRELIN; OBESITY; MELANOCORTIN receptors; BODY mass index; APPETITE; SELF-discrepancy
- Publication
Frontiers in Endocrinology, 2020, Vol 11, p1
- ISSN
1664-2392
- Publication type
Article
- DOI
10.3389/fendo.2020.00437