Polymorphism of the cystatin C gene in patients with acute coronary syndromes: Results from the PLATelet inhibition and patient Outcomes study

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• 作者：Axel Å ; kerblom ; MD ; PhD^a ; ^b ; ^{axel.akerblom@ucr.uu.se" class="auth_mail} ; Niclas Eriksson ; PhD^a ; Lars Wallentin ; MD ; PhD^a ; ^b ; Agneta Siegbahn ; MD ; PhD^c ; Bryan J. Barratt ; PhD^d ; Richard C. Becker ; MD^e ; Andrzej Budaj ; MD ; PhD^f ; Anders Himmelmann ; MD ; PhD^g ; Steen Husted ; MD ; DSc^h ; Robert F. Storey ; MD ; DMⁱ ; Å ; sa Johansson ; PhD^a ; ^j ; Stefan K. James ; MD ; PhD^a ; ^b ; for the PLATO Investigators
• 刊名：American Heart Journal
• 出版年：July 2014
• 年：2014
• 卷：168
• 期：1
• 页码：96-102.e2
• 全文大小：525 K

文摘

Elevated cystatin C concentration is an independent risk factor for cardiovascular (CV) events in patients with acute coronary syndromes. Genetic polymorphisms in CST3 influence cystatin C levels, but their relationship to outcomes is unclear.

Methods

We measured cystatin C concentrations in plasma, obtained within 24 hours of admission, in 16,279 acute coronary syndrome patients from the PLATO trial. In 9,978 patients, we performed a genome-wide association study with up to 2.5 million single nucleotide polymorphisms. Single nucleotide polymorphisms affecting cystatin C levels were evaluated in relation to the first occurrence of myocardial infarction (MI) or CV death within 1 year using Cox regression analysis.

Results

Several single nucleotide polymorphisms were associated with cystatin C levels, most significantly rs6048952 (P = 7.82 × 10⁻¹⁶) adjacent to CST3. Median cystatin C concentrations per genotype were 0.85 mg/L (A/A), 0.80 mg/L (A/G), and 0.73 mg/L (G/G). Modeled as additive, the allelic effect, multivariable adjusted, was −0.045 mg/L per G allele for rs6048952.

The multivariable adjusted c-statistic regarding the combined end point (CV death or MI) was 0.6735. Adding cystatin C or genotype-adjusted cystatin C levels resulted in c-statistics of 0.6761 and 0.6758, respectively.

The multivariable adjusted hazard ratios per G allele at rs6048952 in the entire population were 0.94 (95% CI 0.83–1.06) for CV death or MI and 0.88 (95% CI 0.71–1.08) for CV death.

Conclusions

Genetic polymorphisms affect cystatin C concentrations independently of kidney function. However, the polymorphisms were not observed to be associated with outcome, nor did they improve risk prediction or discriminative models.