Human gain-of-function MC4R variants show signaling bias and protect against obesity

La, Lotta; Mokrosiński, Jacek; E, Mendes de Oliveira; C, Li; Sj, Sharp; Luan, Jian’an; Brouwers, Bas; Ayinampudi,; Bowker, Nicholas; Kerrison, Nicola D.; Kaimakis,; Hoult, Diana; Id, Stewart; Wheeler, Erica F.; Fr, Day; Jrb., Perry; Langenberg, C.J.M.; Wareham, NJ; Is, Farooqi

doi:10.1530/ey.17.11.3

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“…Its gene is located on the long arm of chromosome 18. MC4R is considered an important regulator of food intake and metabolism which dysfunction may be associated with the develop-ment of obesity, insulin resistance, type 2 diabetes and coronary artery disease [4]. Many SNP near the MC4R gene are reported to be associated with an increased risk of obesity [5,6].…”

Section: Introductionmentioning

confidence: 99%

MC4R polymorphism in rs17782313 influences on insulin resistance

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et al. 2021

Medical Research Journal

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Introduction: There are many factors responsible for the development of metabolic syndrome -mainly associated with lifestyle, but also genetic ones. MC4R (melanocortin 4 receptor) genes variants have been associated with the risk of developing obesity, type 2 diabetes mellitus and coronary artery disease.Aim of the study: To investigate the association between MC4R rs17782313 polymorphism and concentrations of glucose, insulin, HOMA-IR and QUICKI values in the whole study group.Materials and methods: Study group consisted of 294 patients (136 men and 158 women). Collected venous blood samples were stored at -70 0 C until the study group was completed. In the laboratory of Clinical Hospital 1 in Zabrze, the DNA materials were isolated, proper concentration of the DNA (15 ng/μL) were prepared and quality and quantity were checked by spectrophotometry. Allelic discrimination was performed with the use of fluorescent-labelled TaqMan Pre-designed SNP Genotyping Assay probes.Results: No statistically significant differences in concentrations of cholesterol, HDL, LDL, TG between genotypes in women and men were observed. In the whole group of patients, glucose and insulin levels did not differ significantly between TT, CT and CC carriers. Significant differences in values of HOMA-IR and QUICKI between TT, CT and CC carriers as well as between TT carriers and CT+CC carriers were found.CC+TT carriers have a significantly lower value of HOMA-IR and higher QUICKI value than TT carriers.Conclusions: MC4R polymorphism in rs17782313 may be associated with insulin resistance. Further studies are necessary to completely assess the association between investigated polymorphism, insulin resistance and risk of diabetes mellitus development.

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Section: Introductionmentioning

confidence: 99%