CYP2C9 genotype and phenotype profile of cross-country skiing athletes

Beste Tacal Aslan; Ozlem Ozge Yilmaz; Tolga Polat; Ipek Yuksel Gozler; Muhammed Fatih Bilici; Omer Kaynar; Korkut Ulucan

doi:10.4103/jnbs.jnbs_36_21

ORIGINAL ARTICLE

Year : 2021 | Volume : 8 | Issue : 3 | Page : 247-250

CYP2C9 genotype and phenotype profile of cross-country skiing athletes

Beste Tacal Aslan¹, Ozlem Ozge Yilmaz¹, Tolga Polat¹, Ipek Yuksel Gozler², Muhammed Fatih Bilici³, Omer Kaynar³, Korkut Ulucan¹
¹ Department of Medical Biology and Genetics, Faculty of Dentistry, Marmara University, Istanbul, Turkey
² Laboratory of Medical Genetics and Molecular Diagnostics, Faculty of Engineering and Natural Sciences, Uskudar University, Istanbul, Turkey
³ Mus Alpaslan University, Department of Physical Education and Sports, Mus, Turkey

Date of Submission	06-Sep-2021
Date of Acceptance	03-Nov-2021
Date of Web Publication	27-Dec-2021

Correspondence Address:
Beste Tacal Aslan
Department of Medical Biology and Genetics, Faculty of Dentistry, Marmara University, Maltepe, Istanbul
Turkey

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jnbs.jnbs_36_21

Abstract

Aim: Most tissues in the body contain cytochrome P450 enzymes, which play an important role in many functions, especially metabolizing drugs and other xenobiotics. The CYP2C9 gene in humans codes for an enzyme called CYP2C9. The goal of this study was to figure out the genotype and allele distributions of the CYP2C9 gene rs1799853 (CYP2C9*2), rs1057910 (CYP2C9*3), rs28371686 (CYP2C9*5) and rs28371685 (CYP2C9*11) polymorphism in our cohort study. Materials and Methods: For this purpose, 19 cross-country skiing athletes took part in our research. After DNAs were extracted from buccal epithelial cells, real-time polymerase chain reaction was used to genotype them. Results: When we looked at the genotype distributions, we found that, the CC genotype was higher than CT and TT genotype for CYP2C9*2. For CYP2C9*3, the AA genotype was higher than the AC genotype and no CC genotype was found. Besides for the CYP2C9*5, only the CC genotype was found. In addition, only the CC genotype was found for CYP2C9*11. For The genotypic and predictive phenotype distribution of CYP2C9 polymorphisms, it was determined that 11 athletes (57.9%) were *1/*1 (extensive metabolizers), and 5 athletes (26.3%) were *1/*2 (intermediate metabolizers). As a poor metabolizer, one athlete *2/*2 (5.3%) and two athlete *2/*3 (10.5%) were determined. Conclusion: This study is the first study investigating the relationship between the CYP2C9 polymorphism in Turkish cross-country skiing athletes.

Keywords: Cross-country skiing athletes, CYP2C9, genetics, polymorphism, sports

How to cite this article:
Aslan BT, Yilmaz OO, Polat T, Gozler IY, Bilici MF, Kaynar O, Ulucan K. CYP2C9 genotype and phenotype profile of cross-country skiing athletes. J Neurobehav Sci 2021;8:247-50

How to cite this URL:
Aslan BT, Yilmaz OO, Polat T, Gozler IY, Bilici MF, Kaynar O, Ulucan K. CYP2C9 genotype and phenotype profile of cross-country skiing athletes. J Neurobehav Sci [serial online] 2021 [cited 2022 Jan 17];8:247-50. Available from: http://www.jnbsjournal.com/text.asp?2021/8/3/247/333761

Introduction

Athletic performance is the combination of an individual's innate genetic gains and skills acquired under the influence of environmental factors.^[1] The determination of gene variants that affect athletic performance, molecular pathways governed by those genes, and predispositions to better athletic performance are all part of sports genetics research.^[2],[3]

Cytochromes are a varied groups of proteins that share only a few characteristics. They are found in almost every type of life, including bacteria, protozoa, yeasts and all higher species. Most cytochromes are proteins that contains heme group involved in electron transfer to produce ATP.^[4] Cytochrome P450 (CYP) is known a group of monooxygenases and is distinct family of cytochromes. CYPs are a superfamily of enzymes that contains heme as a cofactor that functions as a monooxygenase.^[5] Steroids, fatty acids, and xenobiotics are all oxidized by CYP proteins in mammals. Xenobiotic metabolism takes place in two main stages. The main reaction of the first stage (Phase I) is hydroxylation catalyzed by CYP. In addition, CYP is important in hormone synthesis, degradation and cleansing of various compounds.^[6] CYP enzymes involved in active metabolism consist of approximately 99 isoenzymes synthesized from 55 separate gene families.^[7] The human genome contains at least 57 CYP genes. CYP2 functions are drug and steroid metabolism. There are 13 subfamilies and 16 genes such as CYP2A6, CYP2A7, CYP2A13, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6.^[8],[9]

CYP2C9 is an enzyme that in humans is encoded by the CYP2C9 gene. CYP2C9 gene is localized on chromosome 10q24.2. The CYP2C subfamily of human liver microsomal CYP enzymes are known to catalyze the oxidation of mephenytoin and to show genetic variability in drug metabolizing enzymes in humans.^[10] In excess of 2000 changes have been depicted, and certain single nucleotide polymorphisms (SNPs) have been appeared to generally affect CYP action.^[11] Major CYP2C9 variant alleles result in SNP leading to nonanonymous amino acid changes that differ in only a few residues in the coding region: A cytosine to thymine (C > T) rs1799853 polymorphism at base pair 430, encoding for an Arg144Cys amino acid substitution (CYP2C9*2). An adenine to cytosine (A > C) rs1057910 polymorphism at base pair 1075, encoding for an Ile359 Leu amino acid substitution (CYP2C9*3). A cytosine to guanine (C > G) rs28371686 polymorphism at base pair 1080, encoding for an Asp360Glu amino acid substitution (CYP2C9*5). A cytosine to thymine (C > T) rs28371685 polymorphism at base pair 1003, encoding for an Arg335Trp amino acid substitution (CYP2C9*11).^[12]

The purpose of this study is to analyze the distribution of CYP2C9 rs1799853 (*2), rs1057910 (*3), rs28371686 (*5), rs28371685 (*11) polymorphisms and phenotype of CYP2C9 enzyme in Turkish cross-country skiing athletes.

Materials and Methods

Nineteen Turkish cross-country skiing athletes participated in the study. Üsküdar University Ethical Committee permission was obtained for study protocol and performed following the principles of the Declaration of Helsinki II World Medical Association WMA 2018. B.08.6. YÖK.2.ÜS.0.05.0.06 /2013/09, date:07.03.201. Before the study, all the participants signed consent forms containing relevant information such as the study protocol and the intended use and evaluation of the results.

Genotyping

DNA isolations from the buccal cells of the athletes participating in the study were performed with a commercially obtained PureLink DNA isolation kit (Invitrogen, Thermo Fisher Scientific, Inc.). Genotyping of the CYP2C9*2 rs1799853, CYP2C9*3 rs1057910, CYP2C9*5 rs28371686 and CYP2C9*11 rs28371685 polymorphisms were performed using Real-Time polymerase chain reaction on a StepOnePlus (Thermo Fisher Scientific, Inc.) device and Taqman SNP Genotyping Assays genotyping kits according to the manufacturers' protocols (cat. no. 4362691, Thermo Fisher Scientific, Inc.). For a total volume of 10 μl reaction, 5 μl of Genotyping Master Mix (Applied Biosystems, Foster City, CA), 3.5 μl of nuclease-free H2O (Thermofisher, USA), 0.5 μl of genotyping test (Applied Biosystems), and 1 μl of DNA were used. The sequences of the TaqMan Probe used for genotyping are listed in [Table 1].

Table 1: Sequences of the TaqMan probe used for genotyping CYP2C9*2 rs1799853, CYP2C9*3 rs1057910, CYP2C9*5 rs28371686, CYP2C9*11 rs28371685 polymorphisms

Click here to view

Results

In the CYP2C9 analysis, genotypes of CYP2C9*2 was determined in our cohort group that 12 (63.2%) of them had CC, 5 (26.3%) of them CT and 2 (10.5%) had the TT genotype. CYP2C9*3 was determined that 17 (89.5%) of them had AA, and 2 (10.5%) of them had the AC genotype. No CC genotype was found for CYP2C9*3. CYP2C9*5 was determined that all of them (100%) had CC. No CG and GG genotypes were found for CYP2C9*5. CYP2C9*11 was determined that all of them (100%) had CC. No CT and TT genotypes were found for CYP2C9*11.

When allele distributions were studied, CYP2C9*2 was observed that the values were 76.3% for C allele and 23.7% for T allele. CYP2C9*3 was observed that the frequencies were 94.7% for A allele and 5.3% for C allele. CYP2C9*5 was observed that the results were 100% for C allele and CYP2C9*11 was observed that the allelic percentage were 100% for C allele. The genotype and allele number distributions of the athletes are summarized in [Table 2].

Table 2: Genotypic and allelic distribution of the CYP2C9*2 rs1799853, CYP2C9*3 rs1057910, CYP2C9*5 rs28371686 and CYP2C9*11 rs28371685 polymorphisms in the cross-country skiing athletes

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Discussion

High performance in elite athletes improves with environmental factors, training and genetic characteristics.^[13] Investigating the effect mechanisms of genetic parameters on athletes contributes significantly to the regulation of athletic performance of athletes. These genetic parameters affect the physiological, psychological characteristics or nutritional metabolism of the athletes.^[14]

In the human liver, CYP2C9 is one of the most significant drug metabolizing CYP isoforms. CYP2C9 is a catalytic enzyme that catalyzes the metabolism of a wide range of therapeutically significant medications. Changes in the amino acid arrangement of the CYP2C9 enzyme have been demonstrated to alter its activity and substrate selectivity, as well as the metabolism of medications like warfarin.^[15] CYP2C9*2, CYP2C9*3, CYP2C9*5 and CYP2C9*11 Polymorphisms affect not just the metabolic function of CYP, but also the vulnerability to CYP-related disorders.^[16] Clinical trials have been carried out to characterize the contribution of CYP2C9*2 and CYP2C9*3 polymorphisms to pharmacokinetic variability in humans, and major effects have been found for a number of drugs.^[17]

In our study, the CC genotype was higher than CT and TT genotype for CYP2C9*2 rs1799853 polymorphism. Also, when we compared the C allele with the T allele, it was found that the C allele was higher in percentage. For CYP2C9*3 rs1057910 polymorphism, the AA genotype was higher than the AC genotype and no CC genotype was found. At the same time, while comparing the A and C alleles, we discovered that the A allele had a larger percentage. For the CYP2C9*5 rs28371686 polymorphism, only the CC genotype was found. In addition, only the CC genotype was found for the CYP2C9*11 rs28371685 polymorphism. When we looked at our court, it was determined that 11 athletes (57.9%) were *1/*1 (EM), and 5 athletes (26.3%) were *1/*2 (IM). As a PM, one athlete was *2/*2 (5.3%) and two athlete were *2/*3 (10.5%). The genotypic and predictive phenotype distribution of the CYP2C9 polymorphisms in the cross-country skiing athletes are summarized in [Table 3].

Table 3: Genotypic and predictive phenotype distribution of the CYP2C9 polymorphisms in the cross-country skiing athletes

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For the athletes to perform better, metabolisms like vitamin and drug should proceed in proper ways. In which most of the drug metabolism is carried out by CYP2C9. In other words, *1/*1 phenotypes is considered to be an advantage for better athletic performance.

To date, studies including CYP2C9 phenotype and athletes are not enough to speculate on their association. This study is the first study investigating the relationship between CYP2C9 polymorphism distribution and the predictive phenotype in Turkish cross-country skiing athletes. Therefore, there are not many studies that we can compare our findings. Thus, our work will contribute to the genetic information pool and support other studies in this field.

One of the main limitations of the study is the low number of the participants. Our aim was to analyze the athletes at the same level. That was the reason we conduct the study with the same team athletes, who had the same training programs in our study. Another limitation was that we did not perform CYP2C9 metabolite analysis in our cohort. In further studies, we aim to increase the number of athletes and strengthen our data with metabolite analysis.

Patient informed consent

There is no need for patient informed consent.

Ethics committee approval

Üsküdar University Ethical Committee permission was obtained for study protocol and performed following the principles of the Declaration of Helsinki II World Medical Association WMA 2018. B.08.6. YÖK.2.ÜS.0.05.0.06 /2013/09, date:07.03.2013

Financial support and sponsorship

No funding was received.

Conflicts of interest

There are no conflicts of interest to declare.

Author contribution subject and rate

Beste Tacal Aslan(%25): Literature search, data analysis, manuscript preparation, manuscript editing
Özlem Özge Yılmaz (%20): Literature search, experimental studies, manuscript preparation
Tolga Polat (%15): Experimental studies, data analysis, statistical analysis
İpek Yüksel Gözler (%10): Experimental studies
Muhammed Fatih Bilici (%5): Data acquisition
Ömer Kaynar (%5): Data acquisition
Korkut Ulucan (%20): Concept/design of the work, the definition of intellectual content, data analysis, manuscript review.

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