Clinical predictors of weight loss

Abstract

Methods and compositions are generally provided for treating metabolic disorders, e.g., obesity. One aspect discloses methods and compositions for obtaining a biological sample from the subject, evaluating the sample for the presence or absence of a genetic indicator, wherein the genetic indicator is selected from a single nucleotide polymorphism and a level of gene expression, and performing a first metabolic procedure if the genetic indicator is present, or performing an alternative second metabolic procedure if the genetic indicator is absent. One aspect discloses methods and compositions for obtaining a sample including deoxyribonucleic acids (DNA) from the subject, evaluating the DNA for an absence or presence of one or more genetic indicators and performing a first metabolic procedure or an alternative second metabolic procedure based on the absence or presence of the genetic indicator(s). Other aspects are also disclosed.

1 . A method of treating a subject having a metabolic disorder, the method comprising:
 (a) obtaining a biological sample from the subject;   (b) evaluating the sample for the presence or absence of at least one genetic indicator, wherein the at least one genetic indicator is selected from a single nucleotide polymorphism and a level of gene expression within a reference range; and   (c) performing a first metabolic procedure on the subject, if the at least one genetic indicator is absent, or (d) if the at least one genetic indicator is present, performing a second metabolic procedure on the subject, wherein the second metabolic procedure is different from the first metabolic procedure.   
     
     
         2 . A method of treating a weight-related disorder in a subject comprising:
 (a) obtaining a sample comprising nucleic acids from the subject;   (b) evaluating the nucleic acids for an absence or presence of one or more genetic indicators; and   (c) based on if the genetic indicator(s) is absent in (b), performing a first metabolic procedure on the subject, or if the genetic indicator(s) is present in (b), performing a second metabolic procedure on the subject, wherein the second metabolic procedure is different from the first metabolic procedure.   
     
     
         3 . The method of  claim 2 , wherein the second metabolic procedure excludes bariatric surgery. 
     
     
         4 . The method of  claim 2 , wherein the nucleic acids are deoxyribonucleic acids (DNA). 
     
     
         5 . The method of  claim 2 , wherein the nucleic acids are positive for the indicator(s). 
     
     
         6 . The method of  claim 2 , wherein the nucleic acids are negative for the indicator(s). 
     
     
         7 . The method of  claim 2 , wherein the genetic indicator(s) is at least one single nucleotide polymorphism (SNP) selected from the SNPs shown in Table A (SEQ ID NOs 129-837), Table B, or Table C. 
     
     
         8 . The method of  claim 7 , wherein the at least one single nucleotide polymorphism (SNP) is selected from the SNPs shown in Table A. (SEQ ID NOs 129-837). 
     
     
         9 . The method of  claim 7 , wherein the absence of the SNP correlates with therapeutically effective weight loss of at least 20% weight change after the metabolic procedure in the subject. 
     
     
         10 . The method of  claim 2 , further comprising obtaining a clinical measurement in the subject prior to step (c). 
     
     
         11 . The method of  claim 10 , wherein the clinical measurement is at least one of a pre-operative body mass index (BMI), a glucose tolerance, bile acid profile, and body composition/fat distribution of the subject. 
     
     
         12 . The method of  claim 11 , wherein the clinical measurement is the BMI of the subject. 
     
     
         13 . The method of  claim 12 , wherein the nucleic acids are negative for the indicator(s) and the pre-operative BMI of the subject is greater than 23 kg/m 2 . 
     
     
         14 . A method of treating a subject having a metabolic disorder, the method comprising:
 (a) obtaining a biological sample from the subject;   (b) evaluating expression of at least one gene in the sample, wherein the gene is differentially expressed after bariatric surgery;   (c) comparing the expression level of the gene(s) evaluated in (b) to a reference range,   
       if expression of the gene(s) is outside the reference range, performing a first metabolic procedure on the subject, or if expression of the gene is inside the reference range, performing a second metabolic procedure on the subject. 
     
     
         15 . The method of  claim 14 , wherein the second metabolic procedure excludes bariatric surgery. 
     
     
         16 . The method of  claim 14 , wherein the gene(s) are selected from SEQ ID NOs 1-128. 
     
     
         17 . The method of  claim 14 , wherein the reference range of gene expression is ±20% of an average determined from multiple patients having undergone bariatric surgery. 
     
     
         18 . The method of  claim 14 , wherein the first metabolic procedure is a surgical procedure. 
     
     
         19 . The method of  claim 18 , wherein the surgical procedure is selected from the group consisting of gastric bypass, Roux-en-Y gastric bypass (RYGB), biliopancreatic diversion, partial gastrectomy procedures such as vertical sleeve gastrectomy, adjustable gastric banding, duodenal switch, duodenojejunal bypass, vertical banded gastroplasty, intragastric balloon therapy, greater curvature plication, gastric plication, Magenstrasse and Mill, ileal transposition or interposition, small bowel transposition, biliary diversion, procedures involving anastomotic connections of the gastrointestinal tract, gastric balloon implantation and other gastric or intestinal device implantation, gastric, duodenal or intestinal endoluminal barrier implantation, gastric electrical stimulation, small bowel electrical stimulation, vagal electrical stimulation, and vagal electrical inhibition. 
     
     
         20 . The method of  claim 15 , wherein the second metabolic procedure is selected from the group consisting of (a) administering hormone, neuropeptide, receptor agonists or antagonists, (b) other pharmacological or nutritional therapies, (c) activation of brown adipose tissue, and (d) providing an alternative medical device based therapy, such as, but not limited to providing duodenal endoluminal barrier.