The journal of obstetrics and gynaecology research · 2016
Replication of GWAS loci revealed the moderate effect of TNRC6B locus on susceptibility of Saudi women to develop uterine leiomyomas.
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Bondagji Nabeel Saleem, Morad Fatima Amanullah, Al-Nefaei Afnan Abed Abdullah, Khan Imran Ali, Elango Ramu, Abdullah Layla Saleh, M Al-Mansouri Nisma, Sabir Jamal, Banaganapalli Babajan, Edris Sherif, Shaik Noor Ahmad
Аннотация
AIM: 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 χ2 and 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).
CONCLUSION: 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.
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 χ2 and 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).
CONCLUSION: 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.