Genetic Variation in StearoylCoA Desaturase 1 Is Associated with Metabolic Syndrome Prevalence in Costa Rican Adults
Genetic Variation in StearoylCoA Desaturase 1 Is Associated with Metabolic Syndrome Prevalence in Costa Rican Adults
Year: 2011
Authors: Gong, J. Campos, H. McGarvey, S. Wu, Z. Goldberg, R. Baylin, A.
Publication Name: J. Nutr.
Publication Details: Volume 141; Pages 2211 – 2218
Abstract:
Stearoyl CoA desaturase 1 (SCD1) activity, a key regulator of lipid metabolism, may be associated with the development of metabolic syndrome (MetS). We examined the association of genetic variation in the SCD1 gene with the occurrence of MetS and its five components in a population of Costa Rican adults. Associations of tag single nucleotide polymorphisms (tagSNP) of the SCD1 gene with prevalence of MetS and its five components were analyzed by use of log Poisson models with robust variance estimates and linear regression models, respectively. The likelihood ratio was used to test potential gene fatty acid interactive effects with adipose tissue alpha linolenic acid. One tagSNP was significantly associated with an increased prevalence of MetS in the total study sample. Compared with the common homozygous CC genotype, the CT and TT genotypes for rs1502593 were associated with higher prevalence ratios (PR) of MetS for CT vs. CC: and for TT vs. CC. Among women, we observed borderline positive associations between systolic blood pressure and fasting blood sugar levels and rs1502593. Compared to the common haplotype (frequency 5 per cent) with no minor alleles of SCD1 tagSNP, the other two observed common haplotypes carrying the rs1502593 minor allele were significantly associated with elevated prevalence of MetS. No gene fatty acid interactive effects were observed. Our results suggest that genetic variation in the SCD1 gene may play a role in the development of MetS. (Authors abstract)
SCD18, mainly found in adipose and liver tissue, is a key regulator of lipid metabolism. It converts SFA substrates (palmitic acid and stearic acid) to MUFA (palmitoleic acid and oleic acid). SCD1 activity influences plasma HDL and LDL levels in mice and SCD1 null mice have low levels of plasma TG. SCD1 knockout mice are protected from diet induced obesity and insulin resistance even under overfeeding conditions. If these patterns can be extrapolated to humans, then SCD1 might be a potential target to treat metabolic disorders, including obesity and MetS. However, other study results have shown that SCD1 may provide protection against lipotoxicity (i.e., inflammation and insulin resistance) from SFA through converting them into less toxic MUFA. Upregulated SCD1 expression is also inversely correlated with inflammation and insulin resistance in vivo. An inverse relation between elevated SCD1 mRNA levels and insulin resistance was observed among obese and diabetic per insulin resistant patients treated with Rosiglitazone. The objective of the present study was to examine the association between genetic variation in the SCD1 gene and prevalence of MetS using data from a large population based study in Costa Rica. Further, SCD1 expression can be suppressed by ALA and low levels of ALA are associated with increased risk of MetS . A secondary study goal was to explore potential gene fatty acid interactive effects between SCD1 and adipose tissue ALA on the occurrence of MetS. In this study, one tagSNP (rs1502593) of the SCD1 gene that was significantly associated with an increased prevalence for MetS. After correction for multiple testing, this association remained significant. In a stratified analysis according to sex. Significant associations only between rs1502593 and MetS prevalence among women were found. The results suggest that genetic variation in the SCD1 gene may play a role in the development of MetS. Previous studies showed that low levels of ALA are associated with increased risk of MetS. Therefore, interactions between the SCD1 gene and ALA on the risk of MetS could be plausible. However, the authors did not observe either multiplicative or additive interactions between rs1502593 and ALA on the prevalence of MetS. The small sample size in the gene fatty acid interaction analysis may be one reason for no detection of interaction effects. In addition, the categorization process may, however, have contributed to a loss of power to detect additive interaction effects. Thus, more flexible models for testing additive interactions between genes and environmental variables need to be developed. The findings do provide a stimulus for replicating these results in other populations and finding causal genetic variants of the SCD1 gene. In addition, the underlying biological mechanisms of the SCD1 on the development of MetS require further study in different population settings. (Editors comments)
SCD18, mainly found in adipose and liver tissue, is a key regulator of lipid metabolism. It converts SFA substrates (palmitic acid and stearic acid) to MUFA (palmitoleic acid and oleic acid). SCD1 activity influences plasma HDL and LDL levels in mice and SCD1 null mice have low levels of plasma TG. SCD1 knockout mice are protected from diet induced obesity and insulin resistance even under overfeeding conditions. If these patterns can be extrapolated to humans, then SCD1 might be a potential target to treat metabolic disorders, including obesity and MetS. However, other study results have shown that SCD1 may provide protection against lipotoxicity (i.e., inflammation and insulin resistance) from SFA through converting them into less toxic MUFA. Upregulated SCD1 expression is also inversely correlated with inflammation and insulin resistance in vivo. An inverse relation between elevated SCD1 mRNA levels and insulin resistance was observed among obese and diabetic per insulin resistant patients treated with Rosiglitazone. The objective of the present study was to examine the association between genetic variation in the SCD1 gene and prevalence of MetS using data from a large population based study in Costa Rica. Further, SCD1 expression can be suppressed by ALA and low levels of ALA are associated with increased risk of MetS . A secondary study goal was to explore potential gene fatty acid interactive effects between SCD1 and adipose tissue ALA on the occurrence of MetS. In this study, one tagSNP (rs1502593) of the SCD1 gene that was significantly associated with an increased prevalence for MetS. After correction for multiple testing, this association remained significant. In a stratified analysis according to sex. Significant associations only between rs1502593 and MetS prevalence among women were found. The results suggest that genetic variation in the SCD1 gene may play a role in the development of MetS. Previous studies showed that low levels of ALA are associated with increased risk of MetS. Therefore, interactions between the SCD1 gene and ALA on the risk of MetS could be plausible. However, the authors did not observe either multiplicative or additive interactions between rs1502593 and ALA on the prevalence of MetS. The small sample size in the gene fatty acid interaction analysis may be one reason for no detection of interaction effects. In addition, the categorization process may, however, have contributed to a loss of power to detect additive interaction effects. Thus, more flexible models for testing additive interactions between genes and environmental variables need to be developed. The findings do provide a stimulus for replicating these results in other populations and finding causal genetic variants of the SCD1 gene. In addition, the underlying biological mechanisms of the SCD1 on the development of MetS require further study in different population settings. (Editors comments)
