MC4R variant rs17782313 and manifestation of obese phenotype in Pakistani females

Rana, Sobia; Rahmani, Soma; Mirza, Saad

doi:10.1039/c8ra00695d

Cited by 14 publications

(14 citation statements)

References 84 publications

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“…In some of our previous studies, we also reported genderspecific association of the other variants such as MC4R rs17782313, FTO rs9939609, and LEP rs7799039 with overweight/obesity and related anthropometric traits in Pakistani females (29)(30)(31). In comparison to these previously reported associations, the association of NEGR1 rs2815752 observed in the current study has a higher impact (effect size) but less strength.…”

Section: Discussioncontrasting

confidence: 70%

Association of the NEGR1 rs2815752 with obesity and related traits in Pakistani females

Rana

Mobin

2020

Upsala Journal of Medical Sciences

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Introduction: The variant NEGR1 rs2815752 has recently been linked with obesity in Caucasians. However, a very limited number of studies have examined the association of the NEGR1 rs2815752 with overweight/obesity in non-Caucasians with no such study ever performed in Pakistani population. Therefore, the present study was undertaken to seek the association of the rs2815752 with overweight, obesity, and related traits in Pakistanis. Subjects and methods: The study involved 112 overweight/control pairs (total 224) and 194 obese/ control pairs (total 388). Anthropometric parameters were measured by employing standard procedures. Metabolic parameters were determined by biochemical assays. Behavioral information was collected through a questionnaire. The rs2815752 was genotyped via TaqMan allelic discrimination assay. Regression analyses were employed to analyze the data in SPSS software. Results: The study revealed significant gender-specific association of the rs2815752 with obesity (OR 3.03; CI 1.19-7.72, p ¼ 0.020) and some obesity-related anomalous anthropometric traits (weight, BMI, waist circumference, hip circumference, and abdominal and supra-iliac skinfold thicknesses) in females according to dominant model (h ¼ 0.023). However, no association of the rs2815752 with obesityrelated behavioral and metabolic parameters was observed. Conclusion: The NEGR1 rs2815752 may be associated with obese phenotype and some of the related anthropometric traits in Pakistani females.

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Section: Discussioncontrasting

confidence: 70%

Association of the NEGR1 rs2815752 with obesity and related traits in Pakistani females

Rana

Mobin

2020

Upsala Journal of Medical Sciences

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“…The evidence concerning this specific polymorphism that might contribute to overweight and altered feeding patterns is not limited to the populations mentioned above, but it has been also investigated and found in subjects of different nationalities and ethnic origins [ 147 , 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 ], where the majority of these studies addressed the vulnerability of women and children to moderate and severe obesity and aberrant eating behaviors [ 141 , 157 , 161 , 163 ].…”

Section: Melanocortin Receptors In Feedingmentioning

confidence: 99%

The Melanocortin System behind the Dysfunctional Eating Behaviors

et al. 2020

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The dysfunction of melanocortin signaling has been associated with obesity, given the important role in the regulation of energy homeostasis, food intake, satiety and body weight. In the hypothalamus, the melanocortin-3 receptor (MC3R) and melanocortin-4 receptor (MC4R) contribute to the stability of these processes, but MC3R and MC4R are also localized in the mesolimbic dopamine system, the region that responds to the reinforcing properties of highly palatable food (HPF) and where these two receptors seem to affect food reward and motivation. Loss of function of the MC4R, resulting from genetic mutations, leads to overeating in humans, but to date, a clear understanding of the underlying mechanisms and behaviors that promote overconsumption of caloric foods remains unknown. Moreover, the MC4R demonstrated to be a crucial modulator of the stress response, factor that is known to be strictly related to binge eating behavior. In this review, we will explore the preclinical and clinical studies, and the controversies regarding the involvement of melanocortin system in altered eating patterns, especially binge eating behavior, food reward and motivation.

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“…In our previous studies, the aforementioned individual associations were sought using multiple genetic models and in the case of obtaining association in more than one model, the h -index was calculated to indicate the relevant mode of inheritance (such as dominant, recessive, or over-dominant). Also, associations of the two variants FTO rs1421085 24 and TMEM18 rs7561317 25 were obtained without gender stratification while those of the other two namely MC4R rs17782313 23 and NEGR1 rs2815752 26 were observed after gender stratification in females only. Moreover, no association was found for BDNF rs6265 49 .…”

Section: Discussionmentioning

confidence: 90%

“…The current study computes the GRS based on the above-discussed five obesity-linked key loci ( FTO rs1421085, MC4R rs17782313, BDNF rs6265, TMEM18 rs7561317, and NEGR1 rs2815752), which were previously found to be individually associated with obesity and related anthropometric and metabolic measures in the same sample of Pakistani population 23 – 26 . In our previous studies, the aforementioned individual associations were sought using multiple genetic models and in the case of obtaining association in more than one model, the h -index was calculated to indicate the relevant mode of inheritance (such as dominant, recessive, or over-dominant).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the current study has been undertaken to compute the GRS based on five obesity-linked key loci including MC4R rs17782313, BDNF rs6265, FTO rs1421085, TMEM18 rs7561317, and NEGR1 rs2815752 in this at-risk and under-represented population. The aforementioned genetic variants were previously reported to be individually associated with overweight/obesity in large GWASs on western populations 21 , 22 as well as in a sample of Pakistani population 23 – 26 .…”

Section: Introductionmentioning

confidence: 94%

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Predicting anthropometric and metabolic traits with a genetic risk score for obesity in a sample of Pakistanis

Rana

Bhatti

2021

Sci Rep

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Obesity is an outcome of multiple factors including environmental and genetic influences. Common obesity is a polygenic trait indicating that multiple genetic variants act synergistically to influence its expression. We constructed a genetic risk score (GRS) based on five genetic variants (MC4R rs17782313, BDNF rs6265, FTO rs1421085, TMEM18 rs7561317, and NEGR1 rs2815752) and examined its association with obesity-related traits in a sample of Pakistanis. The study involved 306 overweight/obese (OW/OB) and 300 normal-weight (NW) individuals. The age range of the study participants was 12–63 years. All anthropometric and metabolic parameters were measured for each participant via standard procedures and biochemical assays, respectively. The genetic variants were genotyped by allelic discrimination assays. The age- and gender-adjusted associations between the GRS and obesity-related anthropometric and metabolic measures were determined using linear regression analyses. The results showed that OW/OB individuals had significantly higher mean ranks of GRS than NW individuals. Moreover, a significant association of the GRS with obesity-related anthropometric traits was seen. However, the GRS did not appear to affect any obesity-related metabolic parameter. In conclusion, our findings indicate the combined effect of multiple genetic variants on the obesity-related anthropometric phenotypes in Pakistanis.

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MC4R variant rs17782313 and manifestation of obese phenotype in Pakistani females

Abstract: The current study significantly contributes to the knowledge of the genetic proneness to obesity in Pakistani females and could also be helpful for forthcoming meta-analysis studies.

Cited by 14 publications

References 84 publications

Association of the NEGR1 rs2815752 with obesity and related traits in Pakistani females

Association of the NEGR1 rs2815752 with obesity and related traits in Pakistani females

The Melanocortin System behind the Dysfunctional Eating Behaviors

Predicting anthropometric and metabolic traits with a genetic risk score for obesity in a sample of Pakistanis

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