Frequency of genetic variants involved in lipid metabolism and intrahepatic fat

Dear Editor,

An alarming number of pandemics are affecting the world's population, including viral infections, overweight/obesity, and metabolic disorders. Genetic variants may be involved in underlying mechanisms of lipid metabolism and intrahepatic fat accumulation. The minor allele frequencies (MAFs) of variants in the microsomal triglyceride transfer protein (MTTP) gene, which unbalance the concentration of cholesterol, low-density lipoprotein and apolipoprotein B,(^1-3) were investigated in 241 healthy Brazilians.

Data were examined in conjunction with results from the Allele Frequency Aggregator (ALFA) Project (Table 1), in which approximately one million individuals were included.(⁴) The MAFs of H297Q and -493G/T variants were higher in the Brazilian population, possibly indicating a risk for metabolic disorders. These variations may be attributable to the fact that the ALFA Project was composed of a small Latin American population. Brazil has a unique population with evidence of high levels of genetic admixture,(⁵) and we also considered epidemiological data on diversity, which is a challenging aspect of precision medicine.

Table 1
Minor allele frequencies of genetic variants in the microsomal triglyceride transfer protein gene identified in the Brazilian population and in the NCBI SNP database (ALFA Project)

Variant (SNP)	Chr4 position	Allele	MAF				HWE*
			NCBI Global	NCBI Latin American 1	NCBI Latin American 2	Brazilian population
-164T/C (rs1800804)	99574660	T/C	0.26	0.26	0.17	0.27	0.532
-400A/T (rs1800803)	99574424	A/T	0.37	0.46	0.26	0.37	0.212
H297Q (rs2306985)	99594865	C/G (H/Q)	0.39	0.53	0.27	0.50	0.220
-493G/T (rs1800591)	99574331	G/T	0.15	0.00†	0.00	0.33	0.723
I128T (rs3816873)	99583507	T/C (I/T)	0.26	0.28	0.17	0.26	0.277
Q95H (rs61733139)	99583409	G/C (Q/H)	0.05	0.04	0.02	0.09	0.098
Q244E (rs17599091)	99591762	C/G (Q/E)	0.03	0.04	0.01	0.06	0.302

• ^*
  p≥0.05 indicates Hardy-Weinberg equilibrium in the Brazilian population (χ² test); † small sample size (n=68).
• Chr4: chromosome 4; HWE: Hardy-Weinberg equilibrium; Latin American 1: Latin American individuals with Afro-Caribbean ancestry; Latin American 2: Latin American individuals with mostly European and Native American ancestry; MAF: minor allele frequency; NCBI: National Center for Biotechnology Information; SNP: single nucleotide polymorphism.

The study was approved by the Ethics Committee of the Hospital das Clinicas, Universidade de Sao Paulo (CAAE: 57626816.3.0000.0068; #2.779.235).

REFERENCES

• ¹
  Ledmyr H, Karpe F, Lundahl B, McKinnon M, Skoglund-Andersson C, Ehrenborg E. Variants of the microsomal triglyceride transfer protein gene are associated with plasma cholesterol levels and body mass index. J Lipid Res. 2002;43(1):51-8
• ²
  Böhme M, Grallert H, Fischer A, Gieger C, Nitz I, Heid I, Kohl C, Wichmann HE, Illig T, Döring F; KORA Study Cohort. MTTP variants and body mass index, waist circumference and serum cholesterol level: association analyses in 7582 participants of the KORA study cohort. Mol Genet Metab. 2008;95(4):229-32
• ³
  Wang X, Cao Y, Guo J, Li D, Zhang H, Song Q, et al. Association between MTTP genotype (-493G/T) polymorphism and hepatic steatosis in hepatitis C: a systematic review and meta-analysis. Lipids Health Dis. 2023;22(1):154. Review
• ⁴
  Phan L, Jin Y, Zhang H, Qiang W, Shekhtman E, Shao D, et al. "ALFA: Allele Frequency Aggregator." National Center for Biotechnology Information, U.S. National Library of Medicine 2020 [cited 2024 Feb 21]. Available from: http://www.ncbi.nlm.nih.gov/snp/docs/gsr/alfa/
  » http://www.ncbi.nlm.nih.gov/snp/docs/gsr/alfa/
• ⁵
  Pena SD, Santos FR, Tarazona-Santos E. Genetic admixture in Brazil. Am J Med Genet C Semin Med Genet. 2020;184(4):928-38. Review

Associate Editor:

Kenneth Gollob Hospital Israelita Albert Einstein, São Paulo, SP, Brazil ORCID: https://orcid.org/0000-0003-4184-3867

Publication Dates

• Publication in this collection
  20 Sept 2024
• Date of issue
  2024

History

• Received
  19 Mar 2024
• Accepted
  15 Apr 2024