Coronary heart disease (CHD) is a disease in which the heart has insufficient blood supply due to atherosclerosis in the coronary arteries. CHD has become one of the most common chronic diseases threatening the health of the global population. In 2022, approximately 20 million people died from cardiovascular diseases worldwide, of which 9.1 million died from ischemic heart disease.1 The prevalence rate of CHD in China is up to 6.49 %, ‌and it shows a trend of younger in recent years. In 2021, 935,860 people died of heart attacks in China, with an average of 1.78 people dying of heart attacks every minute.2

CHD is a multi-gene inherited disease, with a combination of genetic susceptibility and environmental factor. Lipoprotein(a) [LP (a)], discovered by Berg in 1963, is a special protein with a structure similar to low-density lipoprotein.3 Its structure is mainly composed of one low-density lipoprotein cholesterol (LDL-C) like lipid protein core and two peripheral apolipoproteins, peripheral apolipoprotein a[apo(a)] and apo B-100 (APO B-100) covalently linked by disulfide bonds. Elevated serum LP (a) level is an independent risk factor for CHD, and LP (a) level is mainly regulated by genetics and is almost unaffected by gender, age, environment, diet, statins and exercise.4 The AIM-HIGH trial showed that at the LDL-C of 65.2 mg/dl (1.62 mmol/L) state, the patients with Lp(a) >105 nmol/L (50 mg/dL) were significantly more likely to be affected CHD than patients with Lp (a) below 105 nmol/L. They had a 90 % higher risk of major adverse cardiovascular events.5

Although the specific pathogenesis of the increased risk of CHD caused by elevated LP(a) concentration is not fully understood, since the lipid core in the structure of LP(a) is similar to LDL-C, 88 % of the amino acid sequences in the Apo(a) domain are highly homologous to plasminogen. But it does not have fibrinolytic activity. These structural features make Lp(a) pro-atherogenic and pro-thrombotic.6 LP(a) concentration is related to the molecular weight and concentration of apo(a), and the main active ingredient apo(a) is encoded by the LPA gene. 7 The LPA gene is located on chromosome 6q26-27, is about 135Kb long, contains 40 exons and 39 introns, and causes changes in LP(a) concentration by changing the subtype of apo(a), the number of copies of KIV-2, and the genetic polymorphism of LPA, thereby increasing the risk of CHD. 8

The level of Lp(a) in serum is generally stable, and is not easily affected by diet, drugs or metabolic levels, but is greatly affected by genetic background factors, and has great value for predicting disease risk in families. The rs3798220 is located in the promoter region of LPA gene, 40th exon, which is a T/C mutation. The rs3798220 is associated with development of CHD, and the C allele carriers have a 57 % higher risk of CHD than non-carriers.9 The rs10455872 is located in the 25th intron of the LPA gene and is an A/G mutation. The rs10455872 is one of the most strongly correlated sites with CHD, and the G allele increases the risk of CHD by 1.7 times.10

Multiple studies have shown that carriers of rs3789220 C and rs10455872 G alleles have higher plasma Lp(a) levels. 11,12 Hence, the LPA gene rs3798220 and rs10455872 polymorphisms might have an effect on CHD pathology by increasing plasma Lp(a) concentration. There are many studies on the association of LPA gene rs10455872 and rs3798220 polymorphisms and CHD. However, no consensus has been reached till now. In 2013, Koch et al. reported that the LPA gene rs3798220 and rs10455872 polymorphisms were significantly associated with CHD in a Germany population. 13 The C allele of rs3789220 and G allele of rs10455872 increased the CHD risk respectively. Similarly, in 2024, Tian et al. confirmed this conclusion in a Chinese population. 14 They confirmed that the C allele of rs3789220 and G allele of rs10455872 increased both the CHD risk and in-stent restenosis. By contrast, in 2019, Rouhania et al. did not find a relationship between genomic LPA variants (rs3798220 and rs10455872) and CHD in Iranian population.15 In 2014, Wang et al. also found that the rs3798220 polymorphism had no association with myocardial infarction in a Chinese population.16

The current meta-analysis including 20,231 CHD patients and 35,416 controls from 29 individual researches is performed to explore the relationship between LPA gene rs3798220 and rs10455872 polymorphisms and CHD (Supplement S1).