Genetic Loci ; Humans ; Obesity ; genetics

OBJECTIVETo have a better understanding of genetic contributions to the development of obstructive sleep apnea hypopnea syndrome (OSAHS) by reviewing studies on its genetic basis.

DATA SOURCESA comprehensive search of the PubMed literature without restriction on the publication date was carried out using terms "obstructive sleep apnea" and "candidate genes" or "genetics".

STUDY SELECTIONArticles were selected if they were an original research paper or meta analysis of the genetic factors of OSAHS.

RESULTSFour intermediate phenotypes were described and several candidate genes that may determine the expression and severity of OSAHS were reviewed.

CONCLUSIONMultiple gene-gene interactions occurring in genes that affect obesity, craniofacial structure, ventilator control and asleep-awake pattern may influence the expression of OSAHS in a suitable environment.

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disease characterized by retinopathy, obesity, and polydactyly. So far 21 candidate genes have been discovered, and mutations of such genes can all cause the BBS phenotype. As one of the main features of the disease, the obesity in BBS has been associated with leptin resistance and abnormal adipogenesis. However, its molecular etiology is not yet completely clear. Here the molecular mechanism of BBS-associated obesity is reviewed.
Bardet-Biedl Syndrome ; genetics ; Humans ; Obesity ; genetics ; Phenotype ; Polydactyly ; genetics

INTRODUCTIONObesity is a global pandemic and a major health concern. Obesity is a common but complex, multifactorial disorder with high heritability, where as much as 80% of the variance in the body mass index (BMI) is attributable to genetic factors.

MATERIALS AND METHODSLiterature on the contributing factors of the current obesity epidemic, and genetic basis of human obesity, were reviewed.

RESULTSThe current increasing prevalence of obesity is a relatively recent global event driven by our modern lifestyle and dietary habits. Common obesity is the result of subtle interaction between numerous related genetic variants and environmental factors. The role of the obesity genes in this current epidemic is passive, but its impact is highly significant, because individuals with these genes may be predisposed to severe or even morbid obesity when exposed to the modern "obesogenic" environment.

CONCLUSIONSThe human weight regulation mechanism evolved and becomes efficient in preventing weight loss, but is relatively ineffective in preventing excessive weight gain. The modern "obesogenic" environment encourages a sedentary lifestyle and provides easy access to processed food, which leads to a reduction of energy expenditure and increased caloric intake. We have inadvertently created a biology-environment mismatch, as the human weight regulation is unable to evolve fast enough to keep pace with the environmental change. This resulted in maladaptation of an otherwise sound and metabolically efficient physiological mechanism, with serious metabolic consequences.

In the process of animal fat deposition, the proliferation and differentiation of pre-adipocytes and the change of lipid droplet content in adipocytes are regulated by a series of transcription factors and signal pathways. Although researchers have conducted in-depth studies on the transcriptional regulation mechanisms of adipogenesis, there are relatively few reports on post-transcriptional modification on mRNA levels. The modification of mRNA m⁶A regulated by methyltransferase, demethylase and methylation reading protein is a dynamic and reversible process, which is closely related to fat deposition in animals. Fat mass and obesity associated proteins (FTO) act as RNA demethylases that affect the expression of modified genes and play a key role in fat deposition. This article summarized the mechanism of FTO-mediated demethylation of mRNA m⁶A in the process of animal fat deposition, suggesting that FTO may become a target for effective treatment of obesity. Moreover, this review summarized the development of FTO inhibitors in recent years.
Adipocytes ; Adipogenesis/genetics* ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics* ; Animals ; Obesity/genetics* ; RNA, Messenger/genetics*

Childhood obesity is a global public health problem, which can not only endangers children's health, but also might be an important cause of chronic diseases in adulthood. In recent years, with the in-depth development of precision medicine research, more and more research evidences have shown that there are interactions between environmental factors, such as early intrauterine environment, children's diet, physical activity and children's gene factor on the incidence of childhood obesity, which can result in or inhibit the incidence and development of childhood obesity. This paper summarizes the progress in research in this field to reveal the effects and potential mechanisms of genetic factors and environmental factors on the incidence of childhood obesity in order to provide reference for the precise prevention and control of childhood obesity under different genetic backgrounds.
Child ; Humans ; Pediatric Obesity/genetics* ; Diet ; Causality ; Exercise ; Public Health

Genome, Human ; Genome-Wide Association Study ; Humans ; Obesity ; genetics

The use of atypical antipsychotics is limited by occurrence of adverse reactions such as weight gain, despite of their benefits. This article provides a comprehensive review and discussion of the most significant findings regarding obesity-related pathways and integrates these with the known mechanism of atypical antipsychotic action. The focus of this article is primarily on the genetics of obesity related pathways that may be disrupted by atypical antipsychotics. This review also discussed weight gain, hyperglycemia or occurrence of diabetes while being treated with atypical antipsychotics from the point of view of pharmacogenetics. Pharmacogenetic research seeks to uncover genetic factors that will help clinicians identify the best treatment strategies for their patients. It will aid clinically in the prediction of response and side effects, such as antipsychotic-induced weight gain, and minimize the current "trial and error" approach to prescribing in the near future. This article also presents the genetics of both central and peripheral pathways putatively involved in antipsychotic-induced weight gain while providing a comprehensive review of the obesity literature. This article also review obesity related candidate molecules which may be disrupted during atypical antipsychotic drug treatment.
Antipsychotic Agents ; Genetics ; Humans ; Hyperglycemia ; Obesity ; Pharmacogenetics* ; Weight Gain*

OBJECTIVE: To explore the clinical phenotype and genetic etiology of a child with early-onset severe obesity. METHODS: A child who presented at the Department of Endocrinology, Hangzhou Children's Hospital on August 5, 2020 was selected as the study subject. Clinical data of the child were reviewed. Genomic DNA was extracted from peripheral blood samples of the child and her parents. Whole exome sequencing (WES) was carried out on the child. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: This child was a 2-year-and-9-month girl featuring severe obesity with hyperpigmentation on the neck and armpit skin. WES revealed that she has harbored compound heterozygous variants of the MC4R gene, namely c.831T>A (p.Cys277*) and c.184A>G (p.Asn62Asp). Sanger sequencing confirmed that they were respectively inherited from her father and mother. The c.831T>A (p.Cys277*) has been recorded by the ClinVar database. Its carrier frequency among normal East Asians was 0.000 4 according to the 1000 Genomes, ExAC, and gnomAD databases. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was rated as pathogenic. The c.184A>G (p.Asn62Asp) has not been recorded in the ClinVar, 1000 Genomes, ExAC and gnomAD databases. Prediction using IFT and PolyPhen-2 online software suggested it to be deleterious. Based on the guidelines from the ACMG, it was determined as likely pathogenic. CONCLUSION The c.831T>A (p.Cys277*) and c.184A>G (p.Asn62Asp) compound heterozygous variants of the MC4R gene probably underlay the early-onset severe obesity in this child. Above finding has further expanded the spectrum of MC4R gene variants and provided a reference for the diagnosis and genetic counseling for this family.
Female ; Humans ; Computational Biology ; East Asian People ; Genetic Counseling ; Genomics ; Mutation ; Obesity, Morbid/genetics* ; Child, Preschool ; Pediatric Obesity/genetics*

Klinefelter syndrome is the most common type of genetic cause of hypogonadism. This syndrome is characterized by the presence of 1 or more extra X chromosomes. Phenotype manifestations of this syndrome are small testes, fibrosis of the seminiferous tubules, inability to produce sperm, gynecomastia, tall stature, decrease of serum testosterone and increases of luteinizing hormone and follicle stimulating hormone. Most patients with Klinefelter syndrome are tall, with slender body compositions, and reports of obesity are rare. We report the case of a 35-yr-old man with hypogonadism and morbid obesity and diabetes mellitus. He had gynecomastia, small testes and penis, very sparse body hair and his body mass index was 44.85. He did not report experiencing broken voice and was able to have erections. We conducted a chromosome study. His genotype was 47,X,+t(X;X)(p22.3;p22.3)del(X)(p11.23q11.2). In this case, the patient was diagnosed as Klinefelter syndrome. He showed rare phenotypes like morbid obesity and average height and the phenotype may be caused by the karyotype and the excess number of X chromosome. Further studies of the relationship between chromosomes and phenotype are warranted.
Adult ; Diabetes Complications/genetics ; Humans ; Karyotyping ; Klinefelter Syndrome/*complications/genetics ; Male ; Obesity, Morbid/*complications/genetics ; Phenotype