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- Viljakainen, H., et al.
(författare)
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Low Copy Number of the AMY1 Locus Is Associated with Early-Onset Female Obesity in Finland
- 2015
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Background The salivary alpha-amylase locus (AMY1) is located in a highly polymorphic multi allelic copy number variable chromosomal region. A recent report identified an association between AMY1 copy numbers and BMI in common obesity. The present study investigated the relationship between AMY1 copy number, BMI and serum amylase in childhood-onset obesity. Sixty-one subjects with a history of childhood-onset obesity (mean age 19.1 years, 54% males) and 71 matched controls (19.8 yrs, 45% males) were included. All anthropometric measures were greater in the obese; their mean BMI was 40 kg/m(2) (range 25-62 kg/m(2)) compared with 23 kg/m(2) in the controls (15-32 kg/m(2)). Mean AMY1 copy numbers did not differ between the obese and control subjects, but gender differences were observed; obese men showed the highest and obese women the lowest number of AMY1 copies (p=0.045). Further, only in affected females, AMY1 copy number correlated significantly with whole body fat percent (r=-0.512, p=0.013) and BMI (r=-0.416, p=0.025). Finally, a clear linear association between AMY1 copy number and serum salivary amylase was observed in all subgroups but again differences existed between obese males and females. In conclusion, our findings suggest that AMY1 copy number differences play a role in childhood-onset obesity but the effect differs between males and females. Further studies in larger cohorts are needed to confirm these observations.
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| 2. |
- Pettersson, M., et al.
(författare)
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Copy Number Variants Are Enriched in Individuals With Early-Onset Obesity and Highlight Novel Pathogenic Pathways
- 2017
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 102:8, s. 3029-3039
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Tidskriftsartikel (refereegranskat)abstract
- Context: Only a few genetic causes for childhood obesity have been identified to date. Copy number variants (CNVs) are known to contribute to obesity, both syndromic (15q11.2 deletions, Prader-Willi syndrome) and nonsyndromic (16p11.2 deletions) obesity. Objective: To study the contribution of CNVs to early-onset obesity and evaluate the expression of candidate genes in subcutaneous adipose tissue. Design and Setting: A case-control study in a tertiary academic center. Participants: CNV analysis was performed on 90 subjects with early-onset obesity and 67 normalweight controls. Subcutaneous adipose tissue from body mass index-discordant siblings was used for the gene expression analyses. Main Outcome Measures: We used custom high-density array comparative genomic hybridization with exon resolution in 1989 genes, including all known obesity loci. The expression of candidate genes was assessed using microarray analysis of messenger RNA from subcutaneous adipose tissue. Results: We identified rare CNVs in 17 subjects (19%) with obesity and 2 controls (3%). In three cases (3%), the identified variant involved a known syndromic lesion (22q11.21 duplication, 1q21.1 deletion, and 16p11.2 deletion, respectively), although the others were not known. Seven CNVs in 10 families were inherited and segregated with obesity. Expression analysis of 37 candidate genes showed discordant expression for 10 genes (PCM1, EFEMP1, MAMLD1, ACP6, BAZ2B, SORBS1, KLF15, MACROD2, ATR, and MBD5). Conclusions: Rare CNVs contribute possibly pathogenic alleles to a substantial fraction of children with early-onset obesity. The involved genes might provide insights into pathogenic mechanisms and involved cellular pathways. These findings highlight the importance of CNV screening in children with early-onset obesity.
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