Vitamin D metabolism-related genetic variants, dietary protein intake and improvement of insulin resistance in a 2 year weight-loss trial: POUNDS Lost

Qibin Qi, Yan Zheng, Tao Huang, Jennifer Rood, George A. Bray, Frank M. Sacks, Lu Qi

Research output: Contribution to journalArticle

5 Scopus citations


Aims/hypothesis: Vitamin D and related genetic variants are associated with obesity and insulin resistance. We aimed to examine whether vitamin D metabolism-related variants affect changes in body weight and insulin resistance in response to weight-loss diets varying in macronutrient content. Methods: Three vitamin D metabolism-related variants, DHCR7 rs12785878, CYP2R1 rs10741657 and GC rs2282679, were genotyped in 732 overweight/obese participants from a 2 year weight-loss trial (POUNDS Lost). We assessed genotype effects on changes in body weight, fasting levels of glucose and insulin, and HOMA-IR at 6 months (up to 656 participants) and 2 years (up to 596 participants) in response to low-protein vs high-protein diets, and low-fat vs high-fat diets. Results: We found significant interactions between DHCR7 rs12785878 and diets varying in protein, but not in fat, on changes in insulin and HOMA-IR at both 6 months (p for interaction <0.001) and 2 years (p for interaction ≤0.03). The T allele (vitamin-D-increasing allele) of DHCR7 rs12785878 was associated with greater decreases in insulin and HOMA-IR (p < 0.002) in response to high-protein diets, while there was no significant genotype effect on changes in these traits in the low-protein diet group. Generalised estimating equation analyses indicated significant genotype effects on trajectory of changes in insulin resistance over the 2 year intervention in response to high-protein diets (p < 0.001). We did not observe significant interaction between the other two variants and dietary protein or fat on changes in these traits. Conclusions/interpretation: Our data suggest that individuals carrying the T allele of DHCR7 rs12785878 might benefit more in improvement of insulin resistance than noncarriers by consuming high-protein weight-loss diets. Trial registration: NCT00072995

Original languageEnglish (US)
Pages (from-to)2791-2799
Number of pages9
Issue number12
StatePublished - Sep 29 2015



  • Diet intervention
  • Genetic variants
  • Insulin resistance
  • Vitamin D
  • Weight loss

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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