Erratum: Question Marks Left Over a Quantitative Assessment of Apolipoprotein C3 Gene Polymorphisms.

Dear Editor,

On the occasion of the 2012 annual meeting of the American Society of Human Genetics in San Francisco, the scientific press concluded to a sobering "genetic influences on disease remain hidden" after discussing, among others, the progress made in the field of cardiovascular genetics [1]. In a recent attempt to resolve some of the inconsistent findings, Zhang and coworkers [2] have presented a quantitative analysis of APOC3 variants in coronary heart disease. Unfortunately, only a fraction of the previously published data have been considered and, using the authors’ inclusion criteria, over 10000 alleles are missing from the investigation [3-8]. What is more, incorrect allele counts have led to biased effects for the SstI polymorphism, causing the risk-enhancing allele to become protective [9] and vice versa [10]. Allele counts for the T-455C variant also differ from the published data [11] and are further compromised by duplicates from overlapping samples [11,12]. With regard to both T-455C and C-482T, the vast majority of allele frequencies reported in Table 1 of the article [2] are either in error [11,13-18], missing [12], or entirely fictional [19]. Finally, failure to identify C3175G as a synonym of the SstI polymorphism has led to the omission of more alleles from a publication which served to extract data on T-455C and C-482T [13].

On the whole, the article calls for numerous issues to be ironed out prior to claiming, or to refuting, significant effects of the three APOC3 variants on coronary heart disease susceptibility.

Aging Dis. 2016 Jan 2;7(1):36-44.

doi: 10.14336/AD.2015.0709.

In light of Dr. Sands’ letter, we have reanalyzed data from our meta-analysis of the association between apolipoprotein C-III gene polymorphisms and coronary heart disease (CHD)[1]. Our original database searches did not recover several references cited by Dr. Sand[2-5], which we have now included, and we were unable to extract data useful for our analysis from two other references [6-7]. We have reexamined additional studies referred to by Dr. Sand [8-14] and recalculated our results accordingly.

The new calculations still show an association between the APOC3 SstI polymorphism and CHD under allelic contrast (P <0.0001, OR = 1.17, 95% CI = 1.08-1.27), dominant genetic (P = 0.001, OR = 1.17, 95% CI = 1.07-1.29), and recessive genetic (P = 0.01, OR = 1.36, 95% CI = 1.07-1.73) models; between the APOC3 T-455C polymorphism and CHD under allelic contrast (C vs. T, P = 0.007, OR = 1.19, 95% CI = 1.05-1.35) and dominant genetic (CT+CC vs. TT, P = 0.0004, OR = 1.26, 95% CI = 1.11-1.43), but no longer recessive genetic (CC vs. CT+TT, P = 0.12, OR = 1.25, 95% CI = 0.95-1.66) models; and no association between the APOC3 C-482T polymorphism and CHD under allelic contrast (T vs. C, P = 0.59, OR =1.02, 95%CI = 0.95-1.10), dominant genetic (TT+TC vs. CC, P = 0.17, OR = 1.08, 95% CI = 0.97-1.20)or recessive genetic (TT vs. TC+CC, P = 0.41, OR = 0.94, 95% CI = 0.82-1.09) models. Our meta-analysis suggests that the APOC3 SstI polymorphism significantly increases, the APOC3 T-455C polymorphism may increase, and the APOC3 C-482Tpolymorphism shows no association with CHD susceptibility.

We sincerely apologize for the errors in our article.

PMID: 26816662 [PubMed] PMCID: PMC4723232