ТР53 Codon 72 Polymorphism and Human Papilloma Virus-Associated Cervical Cancer in Kyrgyz Women

Background: The aim of this study was to ascertain the magnitude of association of gene ТР53 Arg72Pro polymorphic marker with cervical cancer (CC) in Kyrgyz women. Methods: We identified and included 205 women of Kyrgyz ethnicity for this case-control study, of whom N=103 were women (mean age 53.5 ± 10.0 years) with histologically confirmed CC and N=102 controls (mean age 46.5 ± 8.5 years). We detected human papilloma virus (HPV) DNA types 16 and 18 using polymerase chain reaction (PCR) with hybridization/fluorescent detection. Genotypes of ТР53 gene Arg72Pro polymorphism were identified using PCR-RFLP assay. Results: Eighty-eight percent (90/103) women with CC had HPV, of whom 43.4% (39/90) had HPV type 16, 24.4% (22/90) had HPV type 18, whereas 32.2% (29/90) carried both types. The univariate analysis of allele and genotype distribution of Arg72Pro polymorphic marker of ТР53 gene showed no difference between CC and control groups (χ2=1.24, р=0.54). However, when CC cases associated with HPV were tested against controls, Arg72 allele and Arg72Arg genotype prevalence were greater compared to controls (χ²=7.25; р=0.027 for genotypes and χ²=6.83; р=0.009 for alleles). In HPV-positive women, Arg72Arg genotype of ТР53 gene was associated with a 1.85-fold increase in the likelihood of CC (OR=1.85 [95% confidence interval (CI) 1.03-3.32]), whereas Arg72 allele increased this likelihood 1.94-fold (OR=1.94 [95% CI 1.20-3.15]). Conclusions: Arg72Arg genotype and Arg72 allele of ТР53 gene in Kyrgyz women increase the risk of HPV-associated CC.

ADIPOQ, KCNJ11 and TCF7L2 polymorphisms in type 2 diabetes in Kyrgyz population: A case-control study.

The aim of this study was to ascertain the polymorphic markers profile of ADIPOQ, KCNJ11 and TCF7L2 genes in Kyrgyz population and to analyze the association of polymorphic markers and combinations of ADIPOQ gene's G276T locus, KCNJ11 gene's Glu23Lys locus and TCF7L2 gene's VS3C>T locus with type two diabetes (T2D) in Kyrgyz population. In this case-control study, 114 T2D patients 109 non-diabetic participants were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Two individual polymorphisms (ADIPOQ rs1501299, KCNJ11 rs5219) were found to be associated with T2D. We found two (Lys23Lys/CC and Glu23Lys/CT) of the overall nine combinations, which were more prevalent in T2D group compared to controls (χ2 = 4.21, P = 0.04). Lys23Lys/CC combination was associated with a 2.65-fold increased likelihood of T2D (OR = 2.65, 95% CI 1.12-6.28), whereas the Glu23Lys/CT combination also increased such likelihood (OR = 3.88, 95% CI 1.27-11.91). This study demonstrated some association of 276T allele and ADIPOQ gene G276T heterozygous genotype as well as KCNJ11 gene 23Lys allele with T2D in ethnic Kyrgyz, but study results should be interpreted with caution because of the limited statistical power.

Mutations of rpoB, katG, inhA and ahp genes in rifampicin and isoniazid-resistant Mycobacterium tuberculosis in Kyrgyz Republic.

BACKGROUND: The aim of this study was to identify mutations of rpoB, katG, inhA and ahp-genes associated Mycobacterium tuberculosis resistance to rifampicin (RIF) and isoniazid (INH) in Kyrgyz Republic. We studied 633 smear samples from the primary pulmonary tuberculosis (TB) patients. We verified Mycobacterium tuberculosis susceptibility to RIF and INH using culture method of absolute concentrations, and commercially available test named "TB-BIOCHIP" (Biochip-IMB, Moscow, Russian Federation). RESULTS: For RIF-resistance, TB-BIOCHIP's sensitivity and specificity were 88% and 97%, 84% and 95% for INH-resistance, and 90% and 97% for multi-drug resistance (MDR). In RIF-resistant strains, TB-BIOCHIP showed mutations in codons 531 (64.8%), 526 (17.3%), 516 (8.1%), 511 (5.4%), 533 (3.2%), 522 (0.6%) and 513 (0.6%) of rpoB gene. The most prevalent was Ser531 > Leu mutation (63.7%). 91.2% of mutations entailing resistance to INH were in katG gene, 7% in inhA gene, and 1.8% in ahpC gene. Ser315→Thr (88.6%) was the most prevalent mutation leading to resistance to INH. CONCLUSIONS: In Kyrgyz Republic, the most prevalent mutation in RIF-resistant strains was Ser531 → Leu in rpoB gene, as opposed to Ser315 → Thr in katG gene in INH-resistant Mycobacterium tuberculosis. In Kyrgyz Republic, the major reservoir of MDR Mycobacterium tuberculosis were strains with combined mutations Ser531 → Leu in rpoB gene and Ser315 → Thr in katG gene. TB-BIOCHIP has shown moderate sensitivity with the advantage of obtaining results in only two days.

The association of Val109Asp polymorphic marker of intelectin 1 gene with abdominal obesity in Kyrgyz population.

BACKGROUND: The aim of this study was to quantify the association of Val109Asp polymorphism of intelectin 1 (ITLN1) gene with the abdominal obesity (AO) in Kyrgyz population. METHODS: Patients admitted to annual screening at a local outpatient facility were enrolled or this study. We genotyped 297 nonrelated adults of Kyrgyz ethnicity, of whom 127 were AO patients, including 46 men and 81 women with the mean age 53.2 ± 7.1 years, and 170 non-obese controls, including 61 men and 109 women with the mean age 52.0 ± 9.0 years. AO was defined as having waist circumferences ≥ 102 cm in men and ≥ 88 cm in women. We used PCR-RFLP method to define Val109Asp polymorphism of ITLN1 gene. RESULTS: Asp109Asp, Asp109Val and Val109Val genotypes were found in 48%, 40%, and 12% of AO patients respectively, and in 53%, 43%, and 4% of controls, whereas Val109Val homozygous genotype of ITLN1 gene Val109Asp polymorphic marker was significantly more prevalent in AO patients. In Kyrgyz population, Val109Val genotype of ITLN1 gene increased the risk of AO (odds ratio (OR) 3.12, 95% CI 1.23-7.90). Asp109Asp homozygous genotype, on opposite, was not associated with this condition (OR 0.82, 95% CI 0.53-1.30). Finally, the allelic variants of Val109Asp polymorphism of ITLN1 gene were not associated with AO. CONCLUSION: Significant increase in the frequency of Val109Val genotype of ITLN1 gene in AO patients may be indicative of some potential role of ITLN1 gene in molding genetic predisposition to AO in the Kyrgyz. This requires further elaboration in the future studies.

The association of polymorphic markers Arg399Gln of XRCC1 gene, Arg72Pro of TP53 gene and T309G of MDM2 gene with breast cancer in Kyrgyz females.

BACKGROUND: The association of genes XRCC1, TP53 and MDM2 with breast cancer (BC) has never been tested in Kyrgyz population. We, therefore, aimed to identify an association of alleles and genotypes of polymorphic markers Arg399Gln of gene XRCC1, Arg72Pro of gene TP53, and T309G of gene MDM2 with the risk of BC in Kyrgyz women. METHODS: This was a case-control study of 219 women of Kyrgyz origin with morphologically verified BC (N = 117) and 102 controls, age-matched with BC cases. The mean age of subjects in this study was 52.2 ± 10.8 years. We extracted DNA from the venous blood and genotyped polymorphic markers Arg399Gln of gene XRCC1, Arg72Pro of gene TP53 and T309G of gene MDM2 using polymerase chain reaction and the method of restriction fragment polymorphism. RESULTS: Allele 399Gln (OR 1.57; 95% CI 1.05-2.35), Arg399Gln of gene XRCC1 heterozygous genotype (OR 2.77; 95% CI 1.60-4.80), the combination of Arg399Gln/Arg72Pro of genes XRCC1/TP53 heterozygous genotype (OR 3.98; 95% CI 1.57-10.09), Arg399Gln/T309G of genes XRCC1/MDM2 (OR 3.0; 95% CI 1.18-7.56), as well as Arg399Gln/Arg72Pro/T309G of genes XRCC1/TP53/MDM2 (OR 6.40; 95% CI 1.18-34.63) were associated with BC in Kyrgyz women. CONCLUSIONS: This is the first study to identify the inter-loci interaction and to find molecular markers of individual risk of BC in Kyrgyz women.