Functional variants in cytochrome b5 type A (CYB5A) are enriched in Southwest American Indian individuals and associate with obesity.
Obesity (Silver Spring)
; 30(2): 546-552, 2022 02.
Article
in En
| MEDLINE
| ID: mdl-35043601
ABSTRACT
OBJECTIVE:
This study aimed to identify genetic variants enriched in Southwest American Indian (SWAI) individuals that associate with BMI.METHODS:
Whole genome sequencing data (n = 296) were used to identify potentially functional variants that are common in SWAI individuals (minor allele frequency ≥10%) but rare in other ethnic groups (minor allele frequency < 0.1%). Enriched variants were tested for association with BMI in 5,870 SWAI individuals. One variant was studied using a luciferase reporter, and haplotypes that included this variant were analyzed for association with various measures of obesity (n = 917-5,870), 24-hour energy expenditure (24-h EE; n = 419), and skeletal muscle biopsy expression data (n = 207).RESULTS:
A 5' untranslated region variant in cytochrome b5 type A (CYB5A), rs548402150, met the enrichment criteria and associated with increased BMI (ß = 2%, p = 0.004). Functionally, rs548402150 decreased luciferase expression by 30% (p = 0.003) and correlated with decreased skeletal muscle CYB5A expression (ß = -0.5 SD, p = 0.0008). Combining rs548402150 with two splicing quantitative trait loci in CYB5A identified a haplotype carried almost exclusively in SWAI individuals that associated with increased BMI (ß = 3%, p = 0.0003) and decreased CYB5A expression, whereas the most common haplotype in all ethnic groups associated with lower BMI and percentage of body fatness, increased 24-h EE, and increased CYB5A expression.CONCLUSIONS:
Further studies on the effects of CYB5A on 24-h EE and BMI may provide insights into obesity-related physiology.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cytochromes b5
/
Obesity
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Obesity (Silver Spring)
Journal subject:
CIENCIAS DA NUTRICAO
/
FISIOLOGIA
/
METABOLISMO
Year:
2022
Document type:
Article
Affiliation country:
United States