Genetic Variation in 9p21 and the Plasma Proteome

Area of Science:

• Genetics
• Proteomics
• Cardiovascular Disease Research

Background:

• Single nucleotide polymorphisms (SNPs) in the 9p21 noncoding region are associated with cardiovascular disease (CVD).
• The underlying mechanisms linking these genetic variants to CVD pathogenesis are not well understood, as the region lacks annotated proteins.

Purpose of the Study:

• To investigate the association between 9p21 genotypes and plasma protein profiles in young adults.
• To explore potential ethnocultural differences in these associations.

Main Methods:

• Genotyping of four specific SNPs in the 9p21 region (rs2383206, rs10757274, rs10757278, rs1333049) in 1611 young adults.
• Measurement of 54 abundant plasma proteins using liquid chromatography-multiple reaction monitoring mass spectrometry.
• Statistical analysis (ANCOVA) to compare plasma protein levels across different genotypes within various ethnocultural groups (Caucasians, East Asians, South Asians).

Main Results:

• In Caucasians, SNPs were associated with apolipoprotein E and haptoglobin-β-chain.
• In East Asians, SNPs correlated with α-1b-Glycoprotein, apolipoprotein B-100, apolipoprotein E, and haptoglobin-β-chain.
• In South Asians, one SNP was linked to apolipoprotein B-100 concentration.

Conclusions:

• 9p21 genotypes are associated with distinct plasma protein profiles in young adults.
• These associations suggest that 9p21 genetic variants may influence CVD risk through various early pathophysiological pathways.
• The identified associations appear to differ among ethnocultural groups, highlighting potential population-specific genetic contributions to CVD risk.