Verification of the Chromosome Region 9q21 Association with Pelvic Organ Prolapse Using RegulomeDB Annotations.
Pelvic organ prolapse (POP) is a common highly disabling disorder with a large hereditary component. It is characterized by a loss of pelvic floor support that leads to the herniation of the uterus in or outside the vagina. Genome-wide linkage studies have shown an evidence of POP association with the region 9q21 and six other loci in European pedigrees. The aim of our study was to test the above associations in a case-control study in Russian population. Twelve SNPs including SNPs cited in the above studies and those selected using the RegulomeDB annotations for the region 9q21 were genotyped in 210 patients with POP (stages III-IV) and 292 controls with no even minimal POP. Genotyping was performed using the polymerase chain reaction with confronting two-pair primers (PCR-CTPP). Association analyses were conducted for individual SNPs, 9q21 haplotypes, and SNP-SNP interactions. SNP rs12237222 with the highest RegulomeDB score 1a appeared to be the key SNP in haplotypes associated with POP. Other RegulomeDB Category 1 SNPs, rs12551710 and rs2236479 (scores 1d and 1f, resp.), exhibited epistatic effects. In this study, we verified the region 9q21 association with POP in Russians, using RegulomeDB annotations.
Laboratory of Ecological Genetics, N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, 3 Gubkin Street, Moscow 117971, Russia.
Maryam B
MB
Khadzhieva
The Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University (MSU), GSP-1, Leninskiye Gory, 1-73, Office 433, Moscow 119991, Russia ; Laboratory of Animal Genetics, N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, 3 Gubkin Street, Moscow 117971, Russia.
Dmitry S
DS
Kolobkov
Department of Obstetrics and Gynecology, Pirogov Russian National Research Medical University, 1 Ostrovitianov Street, Moscow 117997, Russia.
Svetlana V
SV
Kamoeva
Department of Obstetrics and Gynecology, Pirogov Russian National Research Medical University, 1 Ostrovitianov Street, Moscow 117997, Russia.
Anastasia V
AV
Ivanova
Laboratory of Ecological Genetics, N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, 3 Gubkin Street, Moscow 117971, Russia.
Serikbay K
SK
Abilev
Laboratory of Ecological Genetics, N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, 3 Gubkin Street, Moscow 117971, Russia ; Laboratory of Molecular Immunology, Federal Research Center of Pediatric Hematology, Oncology and Immunology Named after Dmitry Rogachev, the Russian Ministry of Health and Social Development, 1 Samora Machel Street, Moscow 117198, Russia.
Lyubov E
LE
Salnikova
D016022:Case-Control Studies; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D006239:Haplotypes; D006801:Humans; D056887:Pelvic Organ Prolapse / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide