TREM2 has a significant, gender-specific, effect on human obesity

Area of Science:

• Immunology
• Genetics
• Metabolic Research

Background:

• Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) is an immune cell membrane protein implicated in neurodegenerative diseases and cancer.
• TREM2 is found on lipid-associated macrophages in adipose tissue, and TREM2 knockout mice exhibit metabolic symptoms.
• Previous research suggests a role for TREM2 in metabolic processes, but its direct involvement in human obesity remains unclear.

Purpose of the Study:

• To investigate the association between TREM2 and human obesity using computational analysis of public databases.
• To explore potential gender-specific roles of TREM2 in obesity.
• To identify genetic variants in TREM2 that may influence Body Mass Index (BMI).

Main Methods:

• Analysis of TREM2 expression levels and BMI correlation in adipose tissue samples from the Genotype-Tissue Expression (GTEx) database.
• Identification and association analysis of a coding single nucleotide polymorphism (SNP) in TREM2 with BMI in the UK Biobank cohort.
• Comparison of the identified TREM2 SNP's association strength with previously known BMI-associated SNPs.

Main Results:

• A significant correlation was found between TREM2 expression levels and BMI in male adipose tissue samples from GTEx.
• A coding SNP in TREM2 (rs2234256, L211P) showed a strong association with BMI in the UK Biobank cohort, particularly in females.
• This TREM2 SNP (rs2234256) demonstrated a more significant association with BMI than previously identified SNPs, with higher BMI in heterozygous and homozygous carriers.

Conclusions:

• TREM2 plays a significant, gender-specific role in human obesity.
• The findings suggest a novel mechanism linking TREM2 to obesity, particularly in females.
• Further research is warranted to elucidate the precise molecular mechanisms underlying TREM2's influence on obesity.