SEX-DIFFERENCES IN TRIGLYCERIDEMIC GENETIC RISK SCORES AND RISK OF MYOCARDIAL INFARCTION.

Aim: Elevated plasma triglyceride (TG) levels are an independent risk factor for the development of cardiovascular disease, including myocardial infarction (MI). Final TG levels are influenced by both environmental (such as dietary habits or physical activity) and genetic factors. We have focused on potential sex differences in the genetic prediction of MI using the TG-associated genetic risk score (GRS).
Methodology: Single nucleotide polymorphisms (SNPs) within 18 genes (GCKR, APOE, APOA5, CAPN3, NAT2, FRMD5, TYW1B, LPL, CYP26A1, LIPC, LRP1, MAP3K1, CTF1, GALNT2, CETP, TRIB1, HLA and CILP2) were genotyped in controls (890 males and 1341 females) and MI patients (913 males and 680 females). Only adults aged between 18 and 65 years at the time of examination were included. Male-specific (mGRS) and female-specific (fGRS) GRSs were created based on the presence of risk alleles for individual SNPs.
Results: In controls, only variants within APOA5 and CILP2 were associated with plasma TG levels in both males and females. SNPs were not consistently associated with an increased risk of MI. Within CAPN3, FRMD5, TYW1B, LPL, and CILP2, the risk alleles differed between males and females. fGRS was not associated with an increased risk of MI in females and was not informative in males. Males with mGRS values over 6 were under increased risk of MI (OR; 95% CI = 1.85; 1.34-2.56; P<0.0005) when compared with subjects with mGRS 3 and less. mGRS was not informative for females (0.84; 0.57-1.25; P=0.40).
Conclusion: The genetic risk of elevated TG seems to be associated with an increased risk of MI only in males. To estimate the genetic risk of MI associated with triglycerides, sex differences must be taken into account and sex-specific GRSs need to be established.

Supported by project No. GIP-23-SL-05-203 (GH, Prague, CR) and by MH CZ - DRO (IKEM, IN 00023001“).