RESUMO
Obesity rates have escalated to the point of a global pandemic with varying prevalence across ethnic groups. These differences are partially explained by lifestyle factors in addition to genetic predisposition to obesity. This review provides a comprehensive examination of the ethnic differences in the genetic architecture of obesity. Using examples from evolution, heritability, admixture, monogenic and polygenic studies of obesity, we provide explanations for ethnic differences in the prevalence of obesity. The debate over definitions of race and ethnicity, the advantages and limitations of multi-ethnic studies and future directions of research are also discussed. Multi-ethnic studies have great potential to provide a better understanding of ethnic differences in the prevalence of obesity that may result in more targeted and personalized obesity treatments.
Assuntos
Etnicidade/genética , Predisposição Genética para Doença , Obesidade/etnologia , Obesidade/genética , Síndrome de Alstrom/etnologia , Síndrome de Alstrom/genética , Síndrome de Bardet-Biedl/etnologia , Síndrome de Bardet-Biedl/genética , Deficiências do Desenvolvimento/etnologia , Deficiências do Desenvolvimento/genética , Dedos/anormalidades , Humanos , Deficiência Intelectual/etnologia , Deficiência Intelectual/genética , Estilo de Vida , Microcefalia/etnologia , Microcefalia/genética , Herança Multifatorial , Hipotonia Muscular/etnologia , Hipotonia Muscular/genética , Miopia/etnologia , Miopia/genética , Síndrome de Prader-Willi/etnologia , Síndrome de Prader-Willi/genética , Prevalência , Degeneração RetinianaRESUMO
PURPOSE: No mutations associated with Alström syndrome (AS), a rare autosomal recessive disease, have been reported in the Japanese population. The purpose of this study was to investigate the genetic and clinical features of two brothers with AS in a consanguineous Japanese family. METHODS: Whole-exome sequencing analysis was performed on two brothers with AS and their unaffected parents. We performed a complete ophthalmic examination, including decimal best-corrected visual acuity, slit-lamp and funduscopic examination, visual-field and color-vision testing, full-field electroretinography, and optical coherence tomography. Fasting blood tests and systemic examinations were also performed. RESULTS: A novel mutation (c.6151C>T in exon 8) in the Alström syndrome 1 (ALMS1) gene that causes a premature termination codon at amino acid 2051 (p.Q2051X), was identified in the homozygous state in the affected brothers and in the heterozygous state in the parents. The ophthalmologic findings for both brothers revealed infantile-onset severe retinal degeneration and visual impairment, marked macular thinning, and severe cataracts. Systemic findings showed hepatic dysfunction, hyperlipidemia, hypogonadism, short stature, and wide feet in both brothers, whereas hearing loss, renal failure, abnormal digits, history of developmental delay, scoliosis, hypertension, and alopecia were not observed in either brother. The older brother exhibited type 2 diabetic mellitus and obesity, whereas the younger brother had hyperinsulinemia and subclinical hypothyroidism. CONCLUSIONS: A novel ALMS1 mutation was identified by using whole-exome sequencing analysis, which is useful not only to identify a disease causing mutation but also to exclude other gene mutations. Although characteristic ophthalmologic findings and most systemic findings were similar between the brothers, the brothers differed slightly in terms of glucose tolerance and thyroid function.
