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Decreased Abdominal Girth and Increased Blood Pressure Associated With a Single Nucleotide Variant of Human Adenylyl Cyclase 6
Author(s) -
Gros Robert,
Van Uum Stan,
HutchinsonJaffe Adam,
Pickering J. Geoffrey,
Hegele Robert A.,
Feldman Ross D.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a795-d
Subject(s) - context (archaeology) , medicine , endocrinology , blood pressure , biology , paleontology
Cyclic AMP is a critical regulator of metabolic and cardiovascular function. However, the role of genetic variability in the regulation of cyclic AMP‐mediated effects is unclear. Therefore, we examined the role of a recently identified genetic variant of AC6 (AC6 S674) in a sample of 364 Caucasian subjects. The AC6 S674 variant was present in 6.6% of subjects. Systolic blood pressure was significantly increased in AC6 S674 subjects (AC6 S674: 113.1±1.3 mmHg, n=25) as compared to wild type AC6 (WT AC6, 109.9±0.6, n=339). Interestingly, there was a significant reduction in waist circumference (by 10%) in subjects carrying the AC6 S674 variant. Further, in circulating fibrocytes taken from 12 wild‐type and 12 variant subjects, AC activity was significantly increased in fibrocytes from AC6 S674 variant subjects (AC6 S674: 117±18 pmol/min/mg, n=12 vs. WT AC6: 63±12 pmol/min/mg, n=12, p<0.05). In rat vascular smooth muscle cells following gene transfer of AC6 S674, AC activity was significantly increased (141±14% of WT AC6, n=12) as compared to cells expressing wild‐type AC6. In the appropriate context, the expression of this novel, relatively common variant of AC6 could influence the development of visceral obesity, the metabolic syndrome and its consequences.