Abstract
To determine whether the integrative variants, haplotypes and diplotypes of the calpain 3 (CAPN3) and the FERM domain containing 5 genes (FRMD5) and several environmental exposures are associated with an implication in lipid homeostasis, which are associated with cardiovascular risk. Genotyping of the CAPN3 rs4344713 and FRMD5 rs524908 was performed by Sanger sequencing in 1,640 subjects (Jing, 819 and Han, 821). Multivariate analyses of covariance models that adjusted by age, gender, body mass index (BMI), blood pressure and lifestyle (smoking and drinking), were constructed using variants, haplotypes and diplotypes of the CAPN3 rs4344713 and FRMD5 rs524908 as predictors and changes in lipid variables. Significant associations with low-density lipoprotein cholesterol and apolipoprotein (Apo) B were found. Linkage disequilibrium with each other showed the haplotype-phenotype associations with triglyceride and ApoA1. This study also suggested pleiotropic associations of the CAPN3-FRMD5 diplotypes with lipid variables. As potential confounders, diastolic blood pressure (DBP) and BMI were significantly associated with lipid variables. We conclude that integrative variants, haplotypes and diplotypes of the CAPN3 rs4344713 and FRMD5 rs524908, as well as DBP and BMI are associated with serum lipid variables in the Jing and Han populations.
Highlights
The calpain 3 gene (CAPN3) contains 24 exons encoding for the 94-kDa Na+/Ca2+-dependent cysteine protease calpain-312,13, which encodes several key mediators of lipid metabolism and oxidative phosphorylation[14]
The levels of total cholesterol (TC), TG and apolipoprotein (Apo) B were significantly higher and those of high-density lipoprotein cholesterol (HDL-C), ApoA1 and the ApoA1/ApoB ratio were significantly lower in the Jing than in the Han participants
We found that the rare variant or minor allele frequency (MAF) of the CAPN3 rs4344713 and FERM domain containing 5 gene (FRMD5) rs524908 were significantly higher in the Jing than in the Han subjects (2.93% vs. 1.58%, P = 0.009 and 21.31% vs. 17.78%, P = 0.011; respectively)
Summary
The CAPN3 contains 24 exons encoding for the 94-kDa Na+/Ca2+-dependent cysteine protease calpain-312,13, which encodes several key mediators of lipid metabolism and oxidative phosphorylation[14]. GWASs have identified hundreds of genetic clues to cardiometabolic disease They are much more likely to be near a gene area closely that causes abnormal cardiometabolic traits, than a sized random set of loci[16]. The ancestors of Jing ethnic group had immigrated from the Vietnam since the 15th century Today, they live in nearby with predominately Han Chinese, the biggest population in China. The typical food of the Jing people is fish soluble, which is called silurid soluble It is the traditional seasoning among the Jing people and is made from different kinds of small fishes which are first pickled before made into the soluble. Jing preserves their custom of intra-ethnic marriage Their genetic background may be less heterogeneous within the population (http://www.chinatravel.com/facts/jing-ethnic-minority.htm). Considering that the CAPN3 and FRMD5 might play an important role on the etiopathogenesis of CVD, we aimed to investigate the possible association of the integrative variants, haplotypes and diplotypes of the CAPN3 rs4344713 and FRMD5 rs524908, as well as several environmental exposures with the lipid homeostasis in the Jing and Han populations
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