Helicobacter pylori infection and cytokine gene polymorphisms in Uzbeks.

Recent studies have reported that Helicobacter pylori (H. pylori) persistent infection and gastric atrophy development were associated with genetic polymorphisms of cytokines. This study aimed to determine possible associations of host genotypes with the seropositivity of anti-H. pylori IgG and anti-CagA IgG, as well as gastric atrophy measured with serum pepsinogens (PG) among an Uzbek population. Subjects were 84 patients with peptic ulcer disease, 35 with other miscellaneous diseases, and 48 healthy persons, for a total of 167 participants. Using a polymerase chain reaction with confronting two-pair primers, their DNA was genotyped for polymorphisms of interleukins (IL) (IL-1B C-31T, IL-2 T-330G, IL-4 C-33T, IL-8 T-251A, IL-10 T-819C, and IL-13 C-1111T) and tumor necrosis factor A (TNF-A) (C-857T and T-1031C). Among 167 participants, 124 (74.9%) were anti-H. pylori IgG seropositive, 142 (85.6%) were anti-CagA IgG seropositive, and 44 (26.3%) exhibited gastric atrophy (PG1 < 70 ng/ml and PG1/PG2<3). The adjusted odds ratio (OR) of IL-4 -33CT for anti-H. pylori IgG seropositivity was significant; OR = 2.33 (95% confidence interval (CI), 1.04-5.19), relative to -33CC. In addition, those with TNF-A-1031TC had a significantly increased risk for anti-H. pylori IgG seropositivity; OR = 2.82 (95% CI, 1.05-7.57), relative to -1031TT. No alleles were associated with the risk of anti-CagA IgG seropositivity or gastric atrophy. The significant associations with cytokine polymorphisms indicated that genetic traits might play a role in the persistent infection of H. pylori among Uzbeks. In addition to confirming the above associations, lifestyle interactions with the genotypes also remain to be elucidated.

Interleukin-8 T-251A polymorphism was associated with positive anti-p53 antibodies in Uzbekistan population.

Interleukin (IL)-8, a proinflammatory chemokine, has been reported to have angiogenic activity and to be responsible for tumor-associated angiogenesis in several cancers. The polymorphism IL-8 T-251A (rs4073) is known to be associated with the expression of IL-8 protein and is related to several cancers. A serum anti-p53 antibody, a new tumor marker, increases in accordance with the mutation of tumor suppressor gene p53. Previous studies have reported the association between IL-8 and p53 mutation in cancer cells or tissues. Therefore, we hypothesized that IL-8 polymorphism might be associated with serum anti-p53 antibody levels. Study subjects were 197 participants (103 males and 94 females, aged 15 to 56 years) who were enrolled in a case-control study on peptic ulcer disease from January to March 2007 in the Uzbekistan Republic. Serum anti-p53 antibody, CEA, and CA19-9 levels were measured, and IL-8 T-251A was genotyped. The A allele frequency in control subjects was 0.48, which is close to the previous reports for Caucasian populations. The proportion of subjects with positive anti-p53 antibodies (higher than 1.3 U/ mL) was greater for AA genotype carriers compared to T allele carriers (17% for AA, and 6% for TA+TT; OR 3.4, p = 0.025 after adjusting for age, sex, comorbidity and ethnicity). Such a difference was not observed for either CEA or CA19-9. We demonstrated that the IL-8 -251 AA genotype was associated with higher anti-p53 antibodies than those of the reference range. Further studies are warranted to clarify whether those with this genotype carrier are susceptible to malignant diseases.

Alcohol dehydrogenase 1B and Aldehyde dehydrogenase 2 Polymorphisms in Uzbekistan.

The alcohol dehydrogenase 1B (ADH1B) -2 (47His) allele and the aldehyde dehydrogenase 2 (ALDH2) - 2 (487Lys) alleles are seen among some Asian peoples, but rare among other ethnic groups. This study examined the allele frequencies in the Uzbekistan Republic, which is located in Central Asia. Subjects were derived from a case-control study on peptic ulcer disease, which included 161 Uzbeks and 23 Russians. They were enrolled at the Republic Research Center of Emergency Medicine located in the capital, Tashkent City. Genotyping was performed for ADH1B Arg47His and ALDH2 Glu487Lys with a polymerase chain reaction using confronting two-pair primers. The frequency for the ADH1B- 2 allele was similar among cases and controls. The ALDH2 -2 allele was rare in both. Among 161 Uzbeks, the ADH1B -2 allele frequency was 0.286 (95% confidence interval, 0.237-0.338) and for the ALDH2 -2 allele was 0.016 (0.005-0.036), while among the 23 Russians the figures were 0.083 (0.024-0.208) and 0.000 (0.000-0.077), respectively. There were no significant differences in drinking habits among individuals with different genotypes, although the ALDH2 -2-2 genotype was not observed. The present study demonstrated that the ADH1B -2 allele frequency among Uzbeks was closer to that among Caucasians than East Asians, some Uzbeks also demonstrating the ALDH2 -2 allele.

Associations between a PTPN11 polymorphism and gastric atrophy--opposite in Uzbekistan to that in Japan.

Src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP-2) of gastric epithelial cells interacts with cagA from Helicobacter pylori (H. pylori). Our previous studies found the AA genotype of a G/A single nucleotide polymorphism at intron 3 (rs2301756) of PTPN11 gene, which encodes SHP-2, to be associated with a lower risk of gastric atrophy. The present study aimed to examine the association with gastric atrophy among the subjects of a case-control study of peptic ulcer disease (PUD) conducted in the Uzbek Republic. Cases were 95 patients (61 males and 34 females) with PUD aged 16 to 85 years. Controls were 102 hospital volunteers (42 males and 60 females) including 42 patients with miscellaneous diseases, aged 15 to 75 years. Gastric atrophy was evaluated with serum pepsinogens (PG1<70 ng/ml and PG1/PG2<3). Polymorphisms of PTPN11 at intron 3 (rs2301756) and intron10 (rs12229892) were genotyped with PCR with confronting two-pair primers (PCR-CTPP). Anti-cagA IgG antibody was detected in 93.7% of cases and 77.5% in controls. Gastric atrophy was observed in 24.2% of the PUD patients and 33.3% in the controls. The A allele at intron 3 was completely linked to the G allele at intron 10. The age, sex, and group (cases and controls) adjusted odds ratio of gastric atrophy was 0.18 (95% confidence interval, 0.04-0.86) for intron 3 GG genotype relative to AA genotype. Since the finding was opposite to that among Japanese, the H. pylori strains and/or lifestyle in Uzbekistan might modify the association.