Resequencing Genomic DNA of Patients With Severe Hypertriglyceridemia (MIM 144650)
Key result
Rare mutations in LPL, APOC2, or APOA5, or the APOA5 p.S19W variant, were present in 41.8% of patients with severe hypertriglyceridemia versus 8.9% of controls (OR 7.4; 95% CI 4.5-12.0).
Why the study?
Do coding sequence variants in LPL, APOC2, and APOA5 genes associate with severe hypertriglyceridemia in nondiabetic adults?
Key Points
- This research aims to define the genetic determinants of severe hypertriglyceridemia by identifying mutations in specific candidate genes.
- Resequenced over 2 million base pairs of genomic DNA from 110 nondiabetic patients with severe hypertriglyceridemia.
- Compared prevalence of coding sequence variants with 472 age- and sex-matched normolipidemic controls.
- Analyzed specific mutations in LPL, APOC2, and APOA5 genes.
- Heterozygous mutations were found in 10.0% of severe HTG patients compared to 0.2% of controls, with an odds ratio (OR) of 52 (95% CI 8.6 to 319).
- The APOA5 p.S19W variant was associated with severe HTG, with a carrier OR of 5.5 (95% CI 3.3 to 9.1).
- Rare mutations or the APOA5 variant were present in 41.8% of HTG subjects, compared to 8.9% of controls, with an OR of 7.4 (95% CI 4.5 to 12.0).
Study Design
Type
Case-Control (n=582)
Structured PICO
Do coding sequence variants in LPL, APOC2, and APOA5 genes associate with severe hypertriglyceridemia in nondiabetic adults?
P
Population
582 adults, comprising 110 nondiabetic patients with severe hypertriglyceridemia and 472 age- and sex-matched normolipidemic controls.
E
Exposure
Resequencing of candidate genes LPL, APOC2, and APOA5
C
Comparator
Normolipidemic controls
O
Outcome
Prevalence of coding sequence variants (missense mutations) in candidate genessurrogate
Main Result
Odds Ratio: 7.4 (95% CI 4.5–12)
Absolute Event Rate: 41.8% vs 8.9%
Rare and common DNA variants in LPL, APOC2, and APOA5 genes are present in a substantial proportion of patients with severe hypertriglyceridemia, highlighting the genetic basis of the disorder.
Authors
Discussion
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Implication
Supports genetic contribution to severe HTG; leaves open whether variant testing alters management in nondiabetic adults.
Cite This Study
Wang et al. (2007) conducted a case-control in Severe hypertriglyceridemia (n=582). Rare mutations in LPL, APOC2, and APOA5 or APOA5 p.S19W variant vs. Normolipidemic controls was evaluated on Prevalence of rare mutations or the APOA5 p.S19W variant (OR 7.4, 95% CI 4.5 to 12.0). Rare mutations in LPL, APOC2, or APOA5, or the APOA5 p.S19W variant, were present in 41.8% of patients with severe hypertriglyceridemia versus 8.9% of controls (OR 7.4; 95% CI 4.5-12.0).