Sex-specific association of FABP2 polymorphisms with the risk of obesity in the Tehran Cardio-Metabolic Genetic Study (TCGS)

Gene. 2023 Aug 5:876:147519. doi: 10.1016/j.gene.2023.147519. Epub 2023 May 30.

Abstract

FABP2 is one of the key genes involved in obesity development across different populations. However, there is no comprehensive report about the FABP2 contribution to obesity incidence among Iranians. Hence, the present study was designed to assess the probable role of FABP2 polymorphisms in obesity incidence in the Tehran Cardio- metabolic Genetic Study (TCGS) representative Iran population. Unrelated adults who had BMI information for at least 3 consecutive phases of the TCGS cohort were included. The control and case groups were defined as individuals who always had long-term persistent normal weight (20 < BMI < 25; n = 1526) and individuals who were long-term persistent obese (30 < BMI < 35; n = 1313), respectively. The logistic regression test was used to assess the possible association between SNPs located in and around the FABP2 gene with obesity. Also, we used Haploview and SHEsis to perform haplotype analysis to detect whether or not this chromosomal region is correlated with obesity. We found a gender-dependent association between the rs10857064 FABP2 and the risk of obesity. The presence of the rs10857064-G allele could significantly increase the risk of obesity only in women, not men (OR = 1.26; 95 % CI: 1.02-1.57; p = 0.03). Through haplotype analysis, we also detected that the TG haplotype containing rs7670862 and rs10857064 could significantly enhance the risk of obesity in women, further supporting the central role of rs10857064 in women's long-term obesity risk. In the current study, we revealed that rs10857064-G FABP2 can significantly predispose women to develop obesity. It highlights the importance of different genetic variants in both genders, which could help us to distinguish more efficient obesity screening tests and treatments based on gender in the future.

Keywords: BMI; FABP2; Persistent obesity; Polymorphism; TCGS.

MeSH terms

  • Adult
  • Fatty Acid-Binding Proteins / genetics
  • Female
  • Genetic Predisposition to Disease*
  • Haplotypes
  • Humans
  • Iran
  • Male
  • Obesity* / genetics
  • Polymorphism, Single Nucleotide

Substances

  • Fatty Acid-Binding Proteins
  • FABP2 protein, human