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23-08-2011 | Cardiometabolic | Article

Influence of SNPs on lipid levels consistent across different races

Abstract

Free abstract

MedWire News: An analysis of the effects of 57 confirmed lipid-associated variants showed that the frequency of these polymorphisms varies significantly across multiple ethnic populations in the USA.

Despite this, the influence of these single-nucleotide polymorphisms (SNPs) on lipid levels was generally consistent across groups, report Man-huei Chang (Centers for Disease Control and Prevention, Atlanta, Georgia, USA) and colleagues in the journal Circulation: Cardiovascular Genetics.

Genome-wide association studies (GWAS) have identified a number of SNPs associated with serum lipid levels.

These studies uncovered a panel of candidate loci for lipid traits such as total cholesterol, low-density lipoprotein (LD) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides.

These studies, however, were largely performed in individuals of European descent, making generalizability to other races and ethnicities difficult.

"To date, it remains unclear whether the exact polymorphisms discovered in populations of European descent are relevant to non-European populations in the US," according to the researchers.

In their study, Chang and colleagues analyzed blood lipid concentrations and their associations with 55 GWAS-identified SNPs and two candidate gene SNPs in the APOE gene in a large population-based survey of US residents.

The survey included non-Hispanic Whites (n=2296), non-Hispanic Blacks (n=1699), and Mexican Americans (n=1713).

Overall, the allele frequencies for all SNPs varied significantly by race, except for rs3764261 in the CETP gene.

"This variation may affect the number of individuals at increased risk for a lipid profile that is itself a risk factor for cardiovascular disease," state Chang and colleagues.

The individual SNPs had very little effect on the lipid levels, and these effects were consistent in non-Hispanic Whites, non-Hispanic Blacks, and Mexican Americans.

Overall, significant associations were more likely to be observed in non-Hispanic Whites and Mexican Americans than in non-Hispanic Blacks.

Among non-Hispanic Whites, more GWAS-validated SNPs were validated (<67%) than in non-Hispanic Blacks (<44%) or Mexican Americans (<44%).

Using a genetic risk score for each of the lipid outcomes, the researchers calculated the cumulative effects of the SNPs on LDL, HDL, and total cholesterol, as well as triglyceride levels.

There was no evidence of a differential effect of the genetic risk score on any of the lipid traits across race.

Finally, the researchers analyzed the genetic and non-genetic contribution to variations in lipid concentrations.

They report that conventional risk factors explain 15% to 30% of the total variation in fully adjusted models. The genetic risk score, when added to these conventional risk factors, explains approximately 1% to 11% of the variation in lipid levels.

"The included SNPs had very small individual effects on lipid levels, and only a small proportion of the total variance in lipids can be explained by the combination of all the SNPs," write the researchers.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2011

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