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.