AQP7, a water/glycerol transporting protein, regulates adipocyte glycerol efflux and influences lipid and glucose homeostasis. Altered AQP7 expression in adults leads to impaired glycerol dynamics, adipocyte hypertrophy, and a predisposition to obesity and diabetes. AQP7 gene promoter variants lead to impaired AQP7-mediated adipocyte glycerol efflux and adipocyte hypertrophy. To assess its possible involvement in childhood obesity and metabolic abnormalities, the AQP7 promoter was studied in order to identify possible mutations and/or polymorphisms in children.
Genomic DNA was extracted from the blood of 61 lean children (BMI < 85%) (46 prepubertal and 15 pubertal) and 41 children with obesity (BMI > 95%) (22 prepubertal and 19 pubertal). The samples were sequenced for AQP7 promoter region - 2580 (2421) to - 1161 (3840) using Automated Sanger sequence analysis.
One novel mutation -2185 (T2816A) was found in an obese prepubertal child with low AQP7 mRNA expression, high levels of serum glycerol, and low serum insulin levels. The novel single nucleotide polymorphisms (SNPs) - 2291 (A2710G), - 2219 (C2782A), - 2091 (C2910A), and – 1932 (G3069A) were identified, together with the previously described SNP – 1884 (C3117T), rs3758268. The heterozygous state and the recessive allele of all four SNPs were related to a positive family history of diabetes mellitus type 2 (p = 0.001).
The novel mutation – 2185 (T2816A) might be associated with the lower gene expression of AQP7 and high levels of serum glycerol that possibly contribute to the obese phenotype. The heterozygous genotype of the four SNPs – 2291 (A2710G), - 2219 (C2782A), - 2091 (C2910A), and – 1884 (C3117T) in children may be related to a familial predisposition to diabetes mellitus type 2.