Identification of CYP19A1 single-nucleotide polymorphisms and their haplotype distributions in a Korean population

Balasmeh

Libyan Journal of Medicine

2017

The present study aimed to identify the NAT2 haplotypes, linkage disequilibrium, and novel NAT2 genetic variants among Jordanian population. We isolated the genomic DNA from 68 healthy, Arab, unrelated Jordanian volunteers to amplify the protein-coding region of NAT2 gene by polymerase chain reaction (PCR). Then, the amplified PCR products were sequenced using Applied Biosystems Model (ABI3730x1). It is found that the allele frequencies of known NAT2 genetic variants 191G>A, 282C>T, 341T>C, 481C>T, 590G>A, and 803A>G were 0.7, 26.5, 48.5, 35.3, 30.9, and 32.4%, respectively. The NAT2 allele frequencies were generally similar to those of white Europeans but different from those of Asian and African populations. The most common NAT2 haplotype was NAT2*5B with a frequency of 29.3%. According to the NAT2 haplotype frequencies, 72% (95% confidence interval 61.4–82.7%) of the volunteers were slow encoding NAT2 haplotype acetylators. The NAT2*5 represented variants 341T>C and 481C>T were in strong but not complete linkage disequilibrium (D′ = 0.8, r 2 = 0.63). In addition, this study found a novel nonsynonymous NAT2 436G>A genetic variant with low frequency (0.7%). However, this novel variant was predicted to be tolerated and not harmful to the NAT2 protein, using in silico prediction tools. It is concluded that the frequency of slow encoding NAT2 haplotype was high among Jordanian volunteers, which may have effects on drug responses and susceptibility to some diseases, such as cancers.

Section: Methodsmentioning

confidence: 99%

Sequence analysis of theN-acetyltransferase 2 gene (NAT2) among Jordanian volunteers

Balasmeh

Libyan Journal of Medicine

2017

“…Allele frequency, Hardy-Weinberg equilibrium, haplotype, and LD were analyzed by SNP Alyze software (version 4.1; Dynacom Co., Ltd., Yokohama, Japan) as described previously (Lee et al, , 2010a. Thirteen SNPs having Ͼ5% frequency were applied to select haplotype tagging SNPs.…”

Section: Methodsmentioning

confidence: 99%

“…Seven representative tagging SNPs were selected on the basis of the exclusion of redundant SNPs displaying high levels of linkage disequilibrium by the Tagger program, which combines the simplicity of pairwise methods with the potential efficiency of multimarker approaches (http://www.broad.mit.edu/mpg/tagger/). A detailed method for tagging SNP selection was described previously (Lee et al, 2010a).…”

Section: Methodsmentioning

confidence: 99%

Discovery of a Novel Allelic Variant of CYP2C8, *CYP2C8**11, in Asian Populations and Its Clinical Effect on the Rosiglitazone Disposition In Vivo

Yeo¹,

Lee²,

Lee³

et al. 2011

Drug Metab Dispos

Self Cite

ABSTRACT:The objectives of this study were to identify the genetic variants of CYP2C8, analyze CYP2C8 single nucleotide polymorphisms (SNPs), and characterize their functional consequences in the CYP2C8 substrate drug rosiglitazone in humans. The direct full sequencing of CYP2C8 genomic DNA was performed in a Korean population (n ‫؍‬ 50). A total of 17 CYP2C8 variants including a novel coding variant (E274Stop) were identified. The novel CYP2C8 E274Stop variant was assigned as CYP2C8*11 by the Human Cytochrome P450 (CYP) Allele Nomenclature Committee. Seventeen SNPs were used to characterize linkage disequilibrium, haplotype structures, and haplotype tagging SNPs. Genotyping for CYP2C8*11 in an extended set of Koreans (n ‫؍‬ 400), whites (n ‫؍‬ 100), Han Chinese (n ‫؍‬ 348), Vietnamese (n ‫؍‬ 100), and African Americans (n ‫؍‬ 93) was performed by a newly developed pyrosequencing method. The frequency of CYP2C8*11 was 0.3% in Koreans, 1% in Vietnamese, and 0.14% in Chinese. However, none of the whites or African Americans contained the CYP2C8*11 allele. Subjects with CYP2C8*1/*11 exhibited higher plasma concentration-time profiles of rosiglitazone than those of nine control subjects carrying CYP2C8*1/*1. The area under the concentrationtime curve and peak plasma concentration of rosiglitazone in individuals carrying CYP2C8*1/*11 (n ‫؍‬ 5) were 54 and 34% higher than the mean values observed in the control subjects carrying CYP2C8*1/*1 (P ‫؍‬ 0.015 and P ‫؍‬ 0.025, respectively). In summary, this is the first report to characterize the allele frequency and haplotype distribution of CYP2C8 in a Korean population, and it provides functional analysis of a new variant CYP2C8*11. Our findings suggest that individuals carrying CYP2C8*11, a null allele found in Asians only, may have lower activity for metabolizing CYP2C8 substrate drugs.

“…Human P450 aromatase is encoded by CYP19 gene, which is composed by 9 translated exons encoding a unique protein of 55 kDa and 11 untranslated exons in the beginning of the gene [13]. Nineteen CYP19 gene variants have been identified, four variants have substitutions in the coding exons, ten variants have substitutions in the untranslated exons, six variants have alterations in the 5′ untranslated region and one in the 3′ prime end [14].…”

Section: Introductionmentioning

confidence: 99%

Aromatase (CYP19) gene variants influence ovarian response to standard gonadotrophin stimulation

Lazaros

Hatzi

Xita

et al. 2011

J Assist Reprod Genet

Purpose The association of cytochrome P450 aromatase gene CYP19(TTTA) n polymorphism with ovarian response to FSH stimulation was explored. Methods Three hundred women undergoing medically assisted reproduction and 300 women with at least one spontaneous pregnancy participated in the study. CYP19(TTTA) n polymorphism was genotyped, while serum hormones were determined. During oocyte retrieval, the follicular size, the follicle and oocyte numbers were recorded. Results Six CYP19(TTTA) n alleles with 7 to 12 repeats were revealed. Women homozygous for long CYP19(TTTA) n alleles presented with lower serum FSH levels at the third day of the menstrual cycle (p<0.001) and higher large follicle numbers (p<0.01), compared to women homozygous for short CYP19(TTTA) n alleles. The CYP19(TTTA) 7 allele was associated with higher serum FSH levels (p< 0.003), with lower total follicle (p<0.02) and large follicle numbers (p<0.03), while CYP19(TTTA) 7 allele-carriers presented more frequently with small follicles than CYP19 (TTTA) 7 allele-non carriers (p<0.01). Conclusions CYP19 genetic variants were associated with ovarian reserve and response to standard gonadotrophin stimulation of women undergoing in vitro fertilization.