Genetic variation in PCSK9 rs505151 and CCL22 rs4359426 polymorphisms may contribute to myocardial infarction susceptibility in a South Indian population, with cumulative genetic burden across these variants associated with increased MI risk.
Key Findings
Results
PCSK9 rs505151 was significantly associated with myocardial infarction susceptibility across allelic and genotypic distributions in a South Indian population.
The study was a case-control design with 400 participants divided into four groups: controls (n=100), MI (n=100), T2DM (n=100), and MI with T2DM (n=100).
Significant associations were observed under both dominant and recessive inheritance models for rs505151.
Multivariable logistic regression confirmed the rs505151 risk genotype was independently associated with MI after adjustment for age, sex, body mass index, and smoking status.
The population studied was specifically a South Indian population, which may limit generalizability to other ethnic groups.
Results
PCSK9 rs11591147 was rare in this South Indian population and showed no significant association with myocardial infarction.
The rs11591147 variant was described as 'rare' in this South Indian cohort.
No significant associations were detected for this variant in any inheritance model tested.
This finding contrasts with the significant association observed for the other PCSK9 variant (rs505151) in the same population.
The rarity of this variant may have limited statistical power to detect associations if present.
Results
CCL22 rs4359426 showed limited evidence of association with myocardial infarction, with a significant effect observed only under the dominant inheritance model.
CCL22 is involved in immune cell recruitment and vascular inflammation, providing a biological rationale for its potential role in MI.
Significant association was observed only under the dominant inheritance model, not under other genetic models tested.
The association was described as showing 'limited evidence,' suggesting a weaker or less consistent signal compared to PCSK9 rs505151.
The study included MI patients both with and without type 2 diabetes mellitus to assess genetic effects across different cardiometabolic contexts.
Results
A combined genetic risk score incorporating PCSK9 and CCL22 variants was associated with increased risk of myocardial infarction.
Combined analysis used a genetic risk score to assess cumulative genetic burden from both PCSK9 and CCL22 polymorphisms.
The cumulative genetic burden involving both PCSK9 and CCL22 variants was associated with an increased risk of MI.
This approach suggests additive or combined effects of lipid-regulatory and immune-related genetic pathways on MI susceptibility.
The genetic risk score methodology allowed for assessment beyond single-variant effects.
Results
Significant differences in clinical and biochemical parameters, including lipid indices and cardiometabolic risk markers, were observed between the four study groups.
Differences were statistically significant at p < 0.05 across groups.
Parameters examined included lipid indices and cardiometabolic risk markers.
The four groups compared were: controls (n=100), MI (n=100), T2DM (n=100), and MI with T2DM (n=100).
These biochemical differences provided the clinical context for interpreting the genetic associations.
Methods
The study design investigated MI risk in a South Indian population, addressing a population with a particularly high burden of MI among individuals with type 2 diabetes mellitus.
Total sample size was 400 participants across four equal groups of 100 each.
The study specifically included a T2DM group and a combined MI with T2DM group to assess genetic effects in diabetic and non-diabetic MI contexts.
PCSK9 was investigated as a key regulator of cholesterol homeostasis, and CCL22 as a mediator of immune cell recruitment and vascular inflammation.
The authors noted that further studies are warranted to validate these associations and clarify their biological and clinical relevance.
What This Means
This research examined whether specific genetic variants in two genes — PCSK9 (which regulates cholesterol) and CCL22 (which is involved in immune system responses and inflammation in blood vessels) — are linked to heart attack (myocardial infarction) risk in people from South India. The study compared 400 people divided into four groups: healthy controls, people who had a heart attack, people with type 2 diabetes, and people who had both a heart attack and type 2 diabetes. The researchers found that one variant in the PCSK9 gene (called rs505151) was significantly associated with increased heart attack risk, even after accounting for other risk factors like age, sex, body weight, and smoking. A second PCSK9 variant (rs11591147) was too rare in this population to show any meaningful association. The CCL22 gene variant showed only weak evidence of association with heart attack risk under one specific statistical model.
When the researchers combined the effects of both genetic variants into a single 'genetic risk score,' they found that carrying risk variants in both genes together was associated with an even greater likelihood of having a heart attack. This suggests that both cholesterol-regulating pathways and immune/inflammatory pathways may work together to influence heart attack risk in South Indian individuals. The clinical measurements — including blood lipid levels and other heart health markers — also differed significantly between the four groups, consistent with the known biology of these conditions.
This research suggests that genetic testing for these variants might one day help identify South Indian individuals at higher risk for heart attacks, particularly in the context of diabetes. However, the study was relatively small (100 people per group), and the authors themselves note that larger follow-up studies are needed to confirm these findings and better understand how these genetic differences biologically influence heart attack risk before any clinical applications could be considered.
Chandra Sekar P, Govindaraj A, Veerabathiran R. (2026). Association of PCSK9 and CCL22 gene polymorphisms with myocardial infarction in a South Indian population.. Functional & integrative genomics. https://doi.org/10.1007/s10142-026-02031-7