Frequencies of obesity susceptibility alleles among ethnically and racially diverse bariatric patient populations.
BACKGROUND
Genetic factors likely play a role in obesity and the outcomes after bariatric surgery. Single nucleotide polymorphisms in or near the insulin-induced gene 2 (INSIG-2), fat mass and obesity-associated gene (FTO), melanocortin 4 receptor gene (MC4R), and proprotein convertase subtilisn/kexin type 1 gene (PCSK-1) have been associated with class III obesity in whites. Minimal data are available regarding the genetic susceptibility to obesity in class III obese nonwhites, especially Hispanics. Our objective was to perform a comparative analysis of 4 common genetic variants (INSIG-2, FTO, MC4R, and PCSK-1) associated with obesity in a diverse population of bariatric surgery patients to determine whether a difference exists by ethnicity (white versus Hispanic). The setting of the study was 2 university hospitals in the United States.


METHODS
Bariatric surgery patients from 2 different institutions were enrolled prospectively, and genotyping was performed. Differences in the distribution of INSIG-2, FTO, MC4R, and PCSK-1 single nucleotide polymorphisms among the different ethnicities (whites and Hispanics) were compared using an additive model (0, 1, or 2 risk alleles). A propensity-matched analysis was used to account for cohort differences.


RESULTS
A total of 1276 bariatric patients were genotyped for the INSIG-2, FTO, MC4R, and PCSK-1 obesity single nucleotide polymorphisms. Statistically significant differences in FTO, INSIG-2, MC4R, and PCSK-1 were seen using an additive model. FTO, PCSK-1, and MC4R (test for trend) remained significantly different in the propensity analysis.


CONCLUSIONS
Significant differences in the frequencies of several common obesity susceptibility variants in or near FTO, PCSK-1, and MC4R were found in white and Hispanic patients with class III obesity undergoing bariatric surgery. Larger studies in more class III obese Hispanics of different nationalities are needed.
Department of Surgery, New York University Medical Center/Bellevue Hospital Center, New York, NY 10016, USA. parikm01@med.nyu.edu
Manish
M
Parikh
Jessica
J
Hetherington
Sheetal
S
Sheth
Jamie
J
Seiler
Harry
H
Ostrer
Glenn
G
Gerhard
Craig
C
Wood
Christopher
C
Still
D000328:Adult; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D050110:Bariatric Surgery; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009479:Neuropeptides / Q000235:genetics*; D009765:Obesity / Q000235:genetics* / Q000601:surgery; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D057216:Propensity Score; D011506:Proteins / Q000235:genetics*; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics*; D044465:White People / Q000235:genetics
C467727:INSIG2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C470072:MC4R protein, human; D008565:Membrane Proteins; D009479:Neuropeptides; C403532:PCSK1N protein, human; D011506:Proteins; D044105:Receptor, Melanocortin, Type 4; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human