Sex, age, and ethnic dependency of lipoprotein variants as the risk factors of ischemic heart disease: a detailed study on the different age-classes and genders in Tehran Cardiometabolic Genetic Study (TCGS)

Hossein Lanjanian,Sajedeh Masjoudi,Maryam Moazzam-Jazi,Maryam S Daneshpour,Mahdi Akbarzadeh,Asiyeh Sadat Zahedi,Leila Najd Hassan Bonab

doi:10.1186/s13293-022-00413-7

Abstract

Biological processes involving environmental and genetic factors drive the interplay between age- and sex-regulating lipid profile. The relation between variations in the LPA gene with increasing the risk of coronary heart disease is dependent on population differences, sex, and age. The present study tried to do a gene candidate association analysis in people with myocardial infarction (MI) in a 22 year cohort family-based longitudinal cohort study, Tehran Cardiometabolic Genetic Study (TCGS). After adjusting p value by the FDR method, only the association of rs6415084 with the MI probability and the age-of-CHD-onset was significant in males in their middle age (p < 0.005). Surprisingly, a lack of association was observed for the rest of the markers (16 SNPs). These results revealed the moderator effects of age and sex on the association between the genetic variants (SNPs) of LPA and heart disease risk. Our observations may provide new insights into the biology that underlies lipid profile with age or the sexual dimorphism of Lp(a) metabolism. Finally, Lp(a) appears to be an independent risk factor; however, the role of sex and ethnicity is important.

Highlights

Elevated lipoprotein (a) is associated with incidence and severity increasing of cardiovascular diseases [1, 2]
The investigation of tertiles Lipoprotein (a) concentration, rs10455872, and rs3798220 with allcause mortality and cardiovascular mortality with the severity of disease in a large-scale study showed that lipoprotein (a) concentrations and the genetic variants have no associations with mortality in patients with prevalent coronary heart disease
Material and methods In the present case–control study, 783 unrelated individuals with MII were selected and compared with the same number of controls. These individuals were assigned from the Tehran Cardiometabolic Genetic Study (TCGS), which is a large-scale family-based longitudinal cohort study [16] that is a subpopulation of the Tehran Lipid and Glucose Study (TLGS) [17]

Summary

Introduction

Elevated lipoprotein (a) is associated with incidence and severity increasing of cardiovascular diseases [1, 2]. In the Chinese Han population, the association of five SNPs (rs1367211, rs3127596, rs9347438, rs6415085, and rs9364559) in the LPA gene with the development of coronary artery disease (CAD) were. A study in a large sample of Brazilian patients confirmed the association of rs10455872 with CAD development, while it showed a lack of association of the rs3798220 with this disease [9]. Heinz Nixdorf Recall’s study provided evidence for the association of LPA rs10455872 with higher Lp(a) and Coronary artery calcification (CAC), a well-proven marker for coronary artery disease and a risk factor for cardiovascular events. The investigation of tertiles Lipoprotein (a) concentration, rs10455872, and rs3798220 with allcause mortality and cardiovascular mortality with the severity of disease in a large-scale study showed that lipoprotein (a) concentrations and the genetic variants have no associations with mortality in patients with prevalent coronary heart disease. The results showed that these variables are not useful risk factors to predict progression to death after coronary heart disease is established [11]

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Discussion

Conclusion