A novel A/G SNP in the-615th position of the dopamine D4 receptor promoter region as a source of misgenotyping of the-616 C/G SNP

作者：Ronai Z; Szantai E; Szmola R; Nemoda Z; Szekely A; Gervai J; Guttman A; Sasvari Szekely M^*

来源：American Journal of Medical Genetics Part B-Neuropsychiatric Genetics, 2004, 126B(1): 74-78.

DOI：10.1002/ajmg.b.20112

• personality
• association study
• -616 C/G
• -615 A/G
• single nucleotide polymorphism (SNP)
• dopamine D4 receptor (DRD4)
• allele-specific amplification

The polymorphic 5' upstream region of the dopamine D4 receptor (DRD4) gene containing several single nucleotide polymorphisms (SNPs) has recently become a focus of association studies in psychiatric genetics. Most SNP genotyping methods are based on the two-step procedure of restriction fragment length polymorphism (RFLP). An alternative technique is a single-step method of allele-specific amplification (ASA), previously introduced for genotyping the -521 C/T SNP of the DRD4 promoter region and applied here for the -616 C/G SNP. Parallel genotyping of individuals with the novel ASA method and the conventionally used Ava II RFLP showed a potential underestimation of the -616 GG genotype frequency by the conventional method. Sequencing the dubious samples clearly demonstrated a novel A/G SNP at the -615th position influencing the Ava II digestion and thus resulting in misgenotyping. To avoid this problem, we introduced the Sau96 I RFLP for the -616 C/G genotyping as this restriction enzyme is not sensitive for the -615 A/G sequence variation. Allele (-616 G=0.48; -616 C=0.52)and genotype (-616 GG=0.25; -616 GC=0.46; -616 CC=0.29) frequencies were determined by both the novel ASA and the Sau96 I methods. The obtained genotype frequencies corresponded to the Hardy-Weinberg equilibrium in our healthy Caucasian sample (N=534, P=0.168). Using these methods, no association was found between the -616 C/G SNP and personality factors of Cloninger's temperament and character inventory (N=153) in our population.

• 出版日期2004-4-1
• 单位河北医科大学