Association of MARC1, ADCY5, and BCO1 Variants with the Lipid Profile, Suggests an Additive Effect for Hypertriglyceridemia in Mexican Adult Men

Abstract

Epidemiological studies have reported that the Mexican population is highly susceptible to dyslipidemia. The MARC1, ADCY5, and BCO1 genes have recently been involved in lipidic abnormalities. This study aimed to analyze the association of single nucleotide polymorphisms (SNPs) rs2642438, rs56371916, and rs6564851 on MARC1, ADCY5, and BCO1 genes, respectively, with the lipid profile in a cohort of Mexican adults. We included 1900 Mexican adults from the Health Workers Cohort Study. Demographic and clinical data were collected through a structured questionnaire and standardized procedures. Genotyping was performed using a predesigned TaqMan assay. A genetic risk score (GRS) was created on the basis of the three genetic variants. Associations analysis was estimated using linear and logistic regression. Our results showed that rs2642438-A and rs6564851-A alleles had a risk association for hypertriglyceridemia (OR = 1.57, p = 0.013; and OR = 1.33, p = 0.031, respectively), and rs56371916-C allele a trend for low HDL-c (OR = 1.27, p = 0.060) only in men. The GRS revealed a significant association for hypertriglyceridemia (OR = 2.23, p = 0.022). These findings provide evidence of an aggregate effect of the MARC1, ADCY5, and BCO1 variants on the risk of hypertriglyceridemia in Mexican men. This knowledge could represent a tool for identifying at-risk males who might benefit from early interventions and avoid secondary metabolic traits.

Divergent role of Mitochondrial Amidoxime Reducing Component 1 (MARC1) in human and mouse

“…In this study we used exome-wide association analysis in over 500,000 individuals to identify several novel rare pLOFs variants in MARC1 with phenotypes similar to previously reported p.Ala165Thr (A165T) and p.Met187Lys (M187K) variants [11][12][13][14][15][16][17][18][19]. We showed p. A165T substitution in MARC1 causes protein instability, leading to the lower MARC1 protein levels in the livers of human carriers of MARC1 p.A165T variant, confirming this variant is a loss of function.…”

“…These studies revealed several missense variants that are associated with lipid accumulation and NAFLD progression [3][4][5][6][7][8][9][10]. Recent genome-wide association studies discovered that common MARC1 missense variants (p. A165T, rs2642438 G>A and p.M187K, rs17850677 T>A) and several rare MARC1 putative loss of function (pLOF) variants (p.R200Ter, p.R305Ter) in humans are associated with decreased liver fat, lower blood ALT, lower alkaline phosphatase, reduced LDL and total cholesterol, as well as protection from all-cause of liver cirrhosis [11][12][13][14][15][16][17][18][19]. MARC1 (mitochondrial amidoxime-reducing component 1, known also as MOSC1 and MTARC1) is a molybdenum containing enzyme anchored on the outer mitochondria membrane.…”

Low Dietary Betaine Intake Is Associated with Increased Blood Cholesterol in Mexican Subjects

“…Of note, it has been reported that the Mexican population is highly susceptible to the development of dyslipidemia [18]. The most common dyslipidemias in Mexico include hypoalphalipoproteinemia, followed by hypertriglyceridemia and hypercholesterolemia [19].…”