title: Replication of GWAS loci revealed the moderate effect of TNRC6B locus on susceptibility of Saudi women to develop uterine leiomyomas.
abstract: OBJECTIVE
  Uterine leiomyomas (UL) are smooth muscular nodes, whose growth is dependant up on the complex interplay of hormones with genes and uterine physiology. Global statistics indicate the role of ethnic and racial background as contributory factors for UL development. Owing to the lack of data, this study aimed to examine the association between genetic polymorphisms and susceptibility of Arab women of developing UL.
  
  
  METHODS
  We genotyped 105 UL patients and 112 healthy controls for five genetic polymorphisms through real time PCR method. The strength of the association between genotype and allele frequencies with risk of developing UL was tested with their χ2and odds ratio (OR) values. The synergistic cooperation between genetic polymorphisms was estimated through multifactor dimensionality reduction assay.
  
  
  RESULTS
  We found that Saudi women with the AG genotype for the rs12484776 polymorphism are at a 2.6-fold higher risk of developing UL compared to those with other genotypes (OR, 2.69; 95% confidence interval [CI]: 1.45-5.00; P < 0.001). This significance persisted even under co-dominant models (i.e., AA vs GG + AG [OR, 2.74; 95%CI: 1.48-5.08; P = 0.001; and AG vs GG + AG [OR, 2.41; 95% CI: 1.33-4.39; P = 0.003). Genotype distribution frequencies for rs1056836, rs7913069, rs2280543, and rs4247357 were not shown to elevate the disease risk (for all tests P > 0.05).
  
  
  CONCLUSIONS
  The rs12484776 significantly contributes to UL risk among Saudi women, both in single and also in synergistic cooperation with rs2280543, rs7913069, and rs1056836 markers. Our results have yielded mixed findings in replicating European- and Japanese-specific UL genetic susceptibility loci among a geographically and culturally distinct population of the Saudi Arabian Peninsula.
authors.affiliation: Department of Obstetrics and Gynecology, King Abdulaziz University Hospital, Jeddah, Saudi Arabia.|Department of Pathology, King Abdulaziz University Hospital, Jeddah, Saudi Arabia.
authors.forename: Nabeel Saleem
authors.initials: NS
authors.lastname: Bondagji
authors.affiliation: Princess Al-Jawahara Al-Brahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.|Genomics and Biotechnology Section, Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Fatima Amanullah
authors.initials: FA
authors.lastname: Morad
authors.affiliation: Princess Al-Jawahara Al-Brahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.|Genomics and Biotechnology Section, Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Afnan Abed Abdullah
authors.initials: AA
authors.lastname: Al-Nefaei
authors.affiliation: Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Imran Ali
authors.initials: IA
authors.lastname: Khan
authors.affiliation: Department of Genetic Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.|Princess Al-Jawahara Al-Brahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Ramu
authors.initials: R
authors.lastname: Elango
authors.affiliation: Department of Pathology, King Abdulaziz University Hospital, Jeddah, Saudi Arabia.
authors.forename: Layla Saleh
authors.initials: LS
authors.lastname: Abdullah
authors.affiliation: Department of Obstetrics and Gynecology, King Abdulaziz University Hospital, Jeddah, Saudi Arabia.
authors.forename: Nisma
authors.initials: N
authors.lastname: M Al-Mansouri
authors.affiliation: Genomics and Biotechnology Section, Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Jamal
authors.initials: J
authors.lastname: Sabir
authors.affiliation: Department of Genetic Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.|Princess Al-Jawahara Al-Brahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Babajan
authors.initials: B
authors.lastname: Banaganapalli
authors.affiliation: Genomics and Biotechnology Section, Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Sherif
authors.initials: S
authors.lastname: Edris
authors.affiliation: Department of Genetic Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.|Princess Al-Jawahara Al-Brahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Noor Ahmad
authors.initials: NA
authors.lastname: Shaik
mesh_terms: D000328:Adult; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007889:Leiomyoma / Q000235:genetics*; D008875:Middle Aged; D016601:RNA-Binding Proteins / Q000235:genetics*; D012529:Saudi Arabia; D014594:Uterine Neoplasms / Q000235:genetics*
chemical_list: D016601:RNA-Binding Proteins; C542384:TNRC6B protein, human
keywords: Saudi women; benign tumor; fibroid; replication study; single nucleotide polymorphism; uterine leiomyoma