The Genetic Basis of Childhood Obesity: A Systematic Review
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Eligibility Criteria
2.3. Literature Search
2.4. Study Selection
2.5. Data Extraction, Outcomes and Data Synthesis
2.6. Validity Assessment
3. Results
4. Discussion
4.1. Central Nervous System and Obesity
4.2. Adipose Tissue and Obesity
4.3. Adipose Tissue Metabolism
4.4. Adipose Tissue Inflammation and Obesity
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Population | Overweight and Obese Children and Adolescents |
---|---|
Intervention | Obesity lifestyle management interventions |
Comparison | Carriers of at-risk genotypes (SNPs or CNVs) for obesity versus non-carriers of at-risk genotypes for obesity |
Outcome | Change of BMI or other measures of body composition |
Inclusion Criteria | Exclusion Criteria |
---|---|
Age ≤ 20 years | Age > 20 years |
Any language | In vitro or animal studies |
Any geographic location | Reviews, editorials, books and book chapters, notes, letters, conference papers, surveys |
Any publication dates | Preventive intervention programs for obesity development |
Species: Humans | Monogenic and/or syndromic obesity |
Obesity lifestyle interventional studies | Investigation for other mutations except SNPs or CNVs |
BMI: overweight/obesity | Studies examining ΒΜΙ and/or body composition change at a time after the end of a lifestyle intervention program |
Common/polygenic obesity | Pharmacological or bariatric surgery obesity management interventions |
Outcomes examined: change in ΒΜΙ and/or body composition in relation to the genotype | Other outcomes examined and not ΒΜΙ and/or body composition change (e.g., gene expression) |
Examining the effect of SNPs and/or CNVs |
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---|---|---|---|---|---|---|---|
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Hagman et al., Pediatr. Diabetes, 2018 [54] | Cohort | 434 (Overall) 214 (FTO genoty**) | USA | 4–20, 12.4 ± 2.7 | 64.5% | 31.3% Prepubertal | CDC |
Heitkamp et al., JAMA Pediatr., 2020 [55] | Cohort | 1198 | Germany | 14.0 ± 2.2 | 56% | N/A | IOTF |
Hollensted et al., Obesity, 2018 [56] | Baseline: Case Control Follow-Up: Cohort | Baseline: Cases: 920 OW/OB Controls: 698 NW Follow-Up: 754 | Denmark | Cases: 11.63 (9.59–13.87) Controls: 12.50 (10.09–15.10) | 57.7% | N/A | Danish Ref. Chart |
Holzapfel et al., Eur. J. Endocrinol., 2011 [57] | Cohort | 310 | Germany | 8–19, 14 ± 2 | 60.3% | N/A | German Ref. Chart |
Knoll et al., Horm. Metab. Res., 2012 [58] | Cohort | 453 | Germany | 10.8 ± 2.6 | 55% | N/A | German Ref. Chart |
Lai et al., Int. J. Biol. Sci, 2013 [59] | Cohort | 88 | China | 14.11 ± 3.63 | 50% | N/A | N/A |
Leite et al., Mortiz, 2017 [60] | Randomized Control Trial | 47 | Brazil | 12–16, 15.05 ± 1.07 | 44.6% | Tanner Stage: 4 or 5 | WHO |
Moleres et al., J. Pediatr., 2012 [61] | Cohort | 168 | Spain | 12–16, 14.6 ± 0.09 | 62% | N/A | IOTF |
Moleres et al., Nutr. Hosp., 2014 [62] | Cohort | 199 | Spain | 12–16, 14.5 ± 0.08 | 61% | N/A | IOTF |
Moraes et al., An. Acad. Bras. Cienc., 2016 [63] | Cohort | 36 Control Group: 17 Intervention Group: 19 | Brazil | 8–16 Control Group: 11.3 ± 1.6 Ιnterventiοn Group: 10.2 ± 2.2 | 58.3% | N/A | CDC |
Müller et al., BMC Med. Genet., 2008 [64] | Baseline: Case Control Follow-Up: Cohort | Baseline: Cases: 519 Children Controls: 178 Adults Follow up: 207 | Germany | Follow-Up: 10.79 ± 2.52 | Follow up: 54.5% | N/A | IOTF |
Reinehr et al., Diabetes, 2008 [65] | Cohort | 293 | Germany | 6–16, 10.8 ± 2.7 | 55% | 51% Prepubertal, 30% Pubertal, 19% Post-Pubertal | IOTF |
Reinehr et al., Arch. Dis. Child., 2009 [66] | Cohort | 280 | Germany | 10.8 (4.5–16.5) | 45% | N/A | German Ref. Chart |
Roth et al., BMC Pediatr., 2013 [67] | Βaseline: Case Control Follow-Up: Longitudinal | 451 (28 OW, 423 OB) 583 Lean Adults | Germany | Children: 12.0 (10.0–13.7) Adults: 25.3 (22.5–26.8) | 54.9% | N/A | IOTF |
Santoro et al., Am. J. Clin. Nutr., 2007 [68] | Baseline: Case Control Follow-Up: Cohort | 184 OB 100 Non-OΒ Controls | Italy | 9.2 ± 2 | 41.8% | 82% Prepubertal | Italian Ref. Chart |
Scherag et al., Obesity, 2011 [69] | Longitudinal Cohort | 401 Children 626 Adults | Germany | 10.74 ± 2.55 | 54.6% | 53.9% Prepubertal | IOTF |
Schum et al., Exp. Clin. Endocrinol. Diabetes, 2012 [70] | Longitudinal | 75 | Germany | 12.6 ± 2.6 | 46.6% | Pubertal: Heterozygous: 55.8% Homozygous: 76.2% | N/A |
Vogel et al., Obes. Facts, 2011 [71] | Baseline: Case Control Follow-Up: Cohort | Baseline Cases: 889 Controls: 442 Follow-Up: 367 | Germany | Baseline: Cases: 10.69 ± 2.98 Controls: 18.31 ± 1.10 Follow-Up: 10.77 ± 2.66 | Baseline: Cases: 53.2% Controls: 61.3% Follow-Up: 55.9% | N/A | IOTF |
Volckmar et al., Exp. Clin. Endocrinol. Diabetes, 2013 [72] | Baseline: Case Control Follow-Up: Cohort | Baseline: Cases: 454 Controls: 435 Follow-Up: 454 | Germany | 6–16, 10.8 ± 2.6 | 55% | N/A | German Ref. Chart |
Zlatohlavek et al., Clin. Biochem., 2013 [73] | Cohort | 357 | Czech Republic | 8–15, 13.7 ± 4.9 | 61% | N/A | N/A |
Zlatohlavek et al., Med. Sci. Monit., 2018 [74] | Cohort | 684 | Czech Republic | 12.7 ± 2.1 | 59% | N/A | N/A |
References | Genes | Main Findings |
---|---|---|
Central nervous system and obesity | ||
Heitkamp et al., JAMA Pediatr., 2020 [55] | CADM2 | The G allele in rs13078960 SNP is associated with decreased BMI-SDS reduction |
Roth et al., BMC Pediatr., 2013 [67] | DRD2 | Homozygosity for the Τ allele in rs18000497 SNP is associated with decreased BMI-SDS reduction |
Heitkamp et al., JAMA Pediatr., 2020 [55] | LMX1B | Homozygosity for the A allele in rs10733682 SNP is associated with greater weight loss |
Hollensted et al., Obesity, 2018 [56] | The T allele in rs3829849 SNP is correlated with decreased BMI-SDS reduction | |
Gajewska et al., Nutrients, 2016 [52] | LEPR | Carrying at least one minor G allele in Q223R together with the wild-type K665N is associated with the greatest weight loss and fat mass reduction |
Corgosinho et al., Neuropeptides, 2017 [49] | Homozygosity for the T allele in rs2767485 SNP is associated with greater BMI reduction | |
Zlatohlavek et al., Clin. Biochem., 2013 [73] | MC4R | Homozygosity for the C allele in s17782313 SNP is associated with greater weight loss outcomes |
Moleres et al., J. Pediatr., 2012 [61] | The C allele in s17782313 SNP is associated with greater BMI and body composition reduction as part of a GRS | |
Vogel et al., Obes. Facts, 2011 [71] | The C allele in rs17782313 SNP or the A allele in rs12970134 SNP in females are associated with more efficient BMI-SDS reduction than in males | |
Santoro et al., Am. J. Clin. Nutr., 2007 [68] | MC3R | The 6Lys allele of rs3746619 and the 81Ile allele of rs3827103 are associated with reduced BMI change |
Adipose tissue and obesity | ||
Heitkamp et al., JAMA Pediatr., 2020 [55] | RPTOR | Homozygosity for the G allele in the rs12940622 SNP is associated with reduced weight loss |
Barbian et al. [48], do Nascimento et al. [51], Müller et al. [64], Moraes et al. [63], Hollensted et al. [56], Scherag et al. [69], Schum et al. [70] | FTO | Τhe rs9939609, rs1421085, rs1558902, rs1421085, rs17817449, rs9939609 SNPs are not associated with BMI or body composition change |
Moleres et al., J. Pediatr., 2012 [61] | The A allele in rs9939609 SNP is associated with greater BMI reduction both individually and as a part of a GRS | |
Reinehr et al., Arch. Dis. Child., 2009 [66] | Homozygosity for the A allele in rs9939609 SNP of FTO together with homozygosity for the C allele in rs7566605 SNP of INSIG2 is associated with decreased BMI reduction | |
Zlatohlavek et al., Clin. Biochem., 2013 [73] | Homozygosity for the G allele in rs17817449 SNP of FTO is associated with greater BMI reduction both individually and in synergy with homozygosity for the C allele in rs17782313 SNP of MC4R | |
Hagman et al., Pediatr. Diabetes, 2018 [54] | Homozygosity for the A allele in rs8050136 SNP is correlated with greater BMI reduction | |
Heitkamp et al., JAMA Pediatr., 2020 [55] | ETS2 | Homozygosity for the C allele in rs2836754 SNP is associated with greater body weight and BMI reduction |
Heitkamp et al., JAMA Pediatr., 2020 [55] | KAT8 | The A allele in rs9925964 SNP is associated with greater BMI-SDS reduction |
Moleres et al., J. Pediatr., 2012 [61] | TMEM1 | The G allele in rs7561317 SNP is associated with greater BMI-SDS and fat mass reduction individually and as a part of a GRS |
Hollensted et al., Obesity, 2018 [56], Scherag et al., Obesity, 2011 [69], Zlatohlavek et al., Med. Sci. Monit., 2018 [74] | The rs4854349, rs4854344, and rs11127485 SNPs are not associated with BMI or body composition change | |
Moleres et al., J. Pediatr., 2012 [61] | PPARγ | The G allele of rs1801282 SNP is associated with a greater BMI and fat mass reduction as part of a GRS |
Scherag et al., Obesity, 2011 [69] | SDCCAG8 | Homozygosity for the T allele in rs10926984 SNP, the T allele in rs12145833 SNP and the C allele in rs2783963 SNP is associated with reduced BMI change |
Heitkamp et al., JAMA Pediatr., 2020 [55] | CPNE8 | The A allele in rs11170468 SNP is associated with resistance to BMI-SDS reduction |
Adipose tissue metabolism | ||
Moleres et al., Nutr. Hosp., 2014 [62] | APOA1 | The A allele in rs670 SNP is associated with greater weight and BMI reduction, while combined analyses with the A allele in rs1800777 SNP explains up to 24% of BMI-SDS amelioration |
Moleres et al., Nutr. Hosp., 2014 [62] | CETP | The A allele in rs1800777 is associated with greater weight and BMI reduction, while combined analyses with the A allele in rs670 SNP explains up to 24% of BMI-SDS amelioration |
Gao et al., Exp. Physiolm., 2015 [53] | LPL | Homozygosity for the G allele in rs283 SNP is associated with greater body fat reduction |
Reinehr et al., Diabetes, 2008 [65], Reinehr et al., Arch. Dis. Child., 2009 [66] | INSIG2 | Homozygosity for the C alle in rs7566605 SNP is associated with lower BMI and BMI-SDS reduction |
Reinehr et al., Arch. Dis. Child., 2009 [66] | Homozygosity for the C allele in rs7566605 SNP of INSIG2 together with homozygosity for the A allele in rs9939609 SNP of FTO is associated with decreased BMI reduction | |
Deram et al., J. Clin. Endocrinol. Metab., 2008 [50] | PLIN1 | The T allele in rs1052700 is associated with greater BMI and body composition change |
Moleres et al., J. Pediatr., 2012 [61] | ADIPOQ | The C allele in rs822395, the G allele in rs2241766, and the T allele in rs1501299 SNPs are associated with a greater BMI and fat mass reduction as part of a GRS |
Gajewska et al., 2016, Nutrients [52] | The rs266729 and rs1686119 SNPs are not associated with BMI or body composition change | |
Adipose tissue inflammation and obesity | ||
Heitkamp et al., JAMA Pediatr., 2020 [55] | IFNGR1 | Homozygosity for the G allele of the rs13201877 SNP is associated with greater weight and BMI reduction |
Heitkamp et al., JAMA Pediatr., 2020 [55] | SLC39A8 | The T allele in rs13107325 SNP is associated with decreased BMI-SDS reduction |
Moleres et al., J. Pediatr., 2012 [61] | IL6 | The G allele in rs1800795 SNP is associated with a greater BMI and fat mass reduction as part of a GRS |
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Vourdoumpa, A.; Paltoglou, G.; Charmandari, E. The Genetic Basis of Childhood Obesity: A Systematic Review. Nutrients 2023, 15, 1416. https://doi.org/10.3390/nu15061416
Vourdoumpa A, Paltoglou G, Charmandari E. The Genetic Basis of Childhood Obesity: A Systematic Review. Nutrients. 2023; 15(6):1416. https://doi.org/10.3390/nu15061416
Chicago/Turabian StyleVourdoumpa, Aikaterini, George Paltoglou, and Evangelia Charmandari. 2023. "The Genetic Basis of Childhood Obesity: A Systematic Review" Nutrients 15, no. 6: 1416. https://doi.org/10.3390/nu15061416