Kondo et al. (2002) identified homozygosity for a missense mutation in the AQP7 gene (G264V; 602974.0001) in a 48-year-old Japanese man who exhibited greatly diminished glycerol release during exercise, despite a normal increase in plasma noradrenaline. The man ... Kondo et al. (2002) identified homozygosity for a missense mutation in the AQP7 gene (G264V; 602974.0001) in a 48-year-old Japanese man who exhibited greatly diminished glycerol release during exercise, despite a normal increase in plasma noradrenaline. The man had a normal body mass index (BMI), as well as normal plasma concentrations of glycerol, glucose, total cholesterol, HDL cholesterol, and triglyceride. In addition, his fertility appeared to be intact, as he had 3 children. Kondo et al. (2002) noted that the normal adiposity and normal plasma glycerol level at rest in this individual suggested the existence of another pathway to maintain plasma glycerol in the resting state. Ceperuelo-Mallafre et al. (2007) screened 178 Spanish individuals, including 37 lean and 90 obese (see 606641) nondiabetics and 14 lean and 37 obese patients with type 2 diabetes (see 125853), for the G264V mutation in the AQP7 gene. Fourteen (8%) of the 178 individuals carried the mutation, and there was no significant difference in its distribution between lean and obese individuals or between diabetics and nondiabetics. The only individual homozygous for G264V was an obese patient with type 2 diabetes who also had glycerol levels below the 10th percentile. Ceperuelo-Mallafre et al. (2007) stated that the low-normal plasma glycerol levels in this patient supported the hypothesis of an alternative glycerol channel in adipocytes. - Body Mass Index Quantitative Trait Locus 17 Prudente et al. (2007) analyzed SNPs in the AQP7 gene in 977 Italian individuals (530 women and 447 men) and initially found an association between a -953A-G promoter SNP and type 2 diabetes (125853) in women; however, that association was no longer significant after adjustment for BMI. The authors observed that women with a GA or GG genotype had a higher BMI than AA women (p = 0.002), and confirmed the association in an independent case-control study of morbid obesity involving 299 women (odds ratio, 1.66; p = 0.04). Functional studies showed that the -953G promoter had reduced transcriptional activity and impaired ability to bind CCAAT/enhancer binding protein-beta (CEBPB; 189965) transcription factor. In addition, AQP7 expression in adipose tissue decreased from AA to AG to GG individuals (p = 0.038).