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Abstract
Human carboxylesterase 1 (CES1) is a serine esterase that hydrolyzes various exogenous compounds. Single nucleotide polymorphisms (SNPs) of CES1 may lead to inter-individual metabolic variability of its substrates. The allele and haplotype frequencies of known SNPs have been demonstrated to vary among ethnic groups. We analyzed genetic variations of CES1 in a Korean population. Direct sequencing of all exons and flanking regions of the CES1 gene was performed on samples obtained from 200 Koreans. We identified 41 SNPs. The most frequent SNPs was −914G>C (frequency: 99.5%), followed by 4256G>A (frequency: 65.8%), −75T>G (frequency: 59.3%). Haplotype analysis using the identified SNPs revealed fifteen haplotypes (≥1% haplotype frequency) in our samples. The most frequent haplotype was Hap1 (frequency: 15.4%). Among the identified 41 SNPs, nine of which are novel variants and 14 SNPs were nonsynonymous variants. Using the functional predictive software PolyPhen-2, the G19V, E221G, and A270S variants were predicted to be most likely damaging to the function and structure of CES1. In-vitro analyses for two of these variants have been previously performed; however, functional evaluation of E221G (11657A>G, rs200707504) still needs to be conducted. Therefore, further studies are warranted to characterize the functional impact of E221G on CES1 activity.
References
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Table 1.
Primers sequences used for the human CES1 gene analysis
Table 2.
Summary of SNPs and their frequencies in the CES1 gene in a Korean population
| CES1: Reference sequence NG_012057.1 | |||||
|---|---|---|---|---|---|
| SNP (NT change) | Location | CDS change ∗ | Amino Acid substitution | rs ID † | Allelic frequency (%) |
| –1114G>A | 5'UTR | – | – | rs34428341 | 10.3 |
| –914G>C | 5'UTR | – | – | rs28759040 | 99.5 |
| –757delC | 5'UTR | – | – | rs57810510 | 35.3 |
| –722G>A‡ | 5'UTR | – | – | – | 0.3 |
| –610G>A‡ | 5'UTR | – | – | – | 0.3 |
| –322T>G‡ | 5'UTR | – | – | – | 0.3 |
| –161A>G‡ | Exon01 (5'UTR) | – | – | – | 0.3 |
| –75T>G | Exon01 (5'UTR) | – | – | rs3815583 | 59.3 |
| –46A>G | Exon01 (5'UTR) | – | – | rs12149373 | 25.3 |
| –39A>G | Exon01 (5'UTR) | – | – | rs12149371 | 25.3 |
| –30G>A | Exon01 (5'UTR) | – | – | rs144950224 | 1.0 |
| –21G>C | Exon01 (5'UTR) | – | – | rs12149322 | 25.3 |
| –20A>G | Exon01 (5'UTR) | – | – | rs12149370 | 25.3 |
| –2C>G | Exon01 (5'UTR) | – | – | rs12149368 | 24.8 |
| 11G>C | Exon01 | 11G>C | R4P | rs111604615 | 24.8 |
| 15C>T‡ | Exon01 | 15C>T | A5A | – | 24.8 |
| 16T>C | Exon01 | 16T>C | F6L | rs201577108 | 24.8 |
| 19A>G | Exon01 | 19A>G | I7V | rs114788146 | 24.8 |
| 34T>G | Exon01 | 34T>G | S12A | rs12149366 | 24.8 |
| 68A>G | Intron01 | – | – | rs12149359 | 24.8 |
| 73insT | Intron01 | – | – | rs56278207 | 36.0 |
| 4067A>C | Intron01 | – | – | rs3826189 | 1.5 |
| 4085G>T | Exon02 | 56G>T | G19V | rs3826190 | 1.5 |
| 4256G>A | Exon02 | 227G>A | S76N | rs2307240 | 3.3 |
| 4363C>T | Intron02 | – | – | rs3848300 | 65.8 |
| 6635A>G | Intron02 | – | – | rs143802684 | 0.5 |
| 11607C>A | Exon05 | 612C>A | D204E | rs2307227 | 0.3 |
| 11657A>G | Exon05 | 662A>G | E221G | rs200707504 | 2.0 |
| 11720C>G | Intron05 | – | – | rs2307234 | 0.3 |
| 12630C>T | Exon06 | 747C>T | G249G | rs202228585 | 0.5 |
| 13423G>T | Exon07 | 808G>T | A270S | rs115629050 | 0.8 |
| 13447A>G | Exon07 | 832A>G | T278A | rs200489319 | 0.3 |
| 16094A>G‡ | Exon08 | 907A>G | K303E | – | 0.3 |
| 19917G>A | Intron08 | – | – | rs3859093 | 41.3 |
| 19923T>C | Intron08 | – | – | rs3859092 | 41.3 |
| 22041T>G | Intron09 | – | – | rs2302722 | 41.5 |
| 22280C>T‡ | Intron10 | – | – | – | 0.3 |
| 22351C>T | Intron10 | – | – | rs146930283 | 17.3 |
| 22359C>A | Intron10 | – | – | rs147989545 | 42.0 |
| 22445A>T‡ | Exon11 | 1224A>T | T408T | – | 0.3 |
| 26503C>A‡ | Intron11 | – | – | – | 0.3 |
| SNPs: single nucleotide polymorphisms, CES1: carboxylesterase. 1. | |||||
Table 3.
Summary of haplotypes and their frequencies in the CES1 gene in a Korean population
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