Background: Interleukin 10 (IL-10), a cytokine that regulates inflammation, is involved in multiple myeloma (MM) cell proliferation and survival. However, it is unclear whether IL-10 polymorphisms alter the susceptibility to MM. We examined the single nucleotide polymorphism located within the promoter region of IL-10 genes in Japanese patients with MM and monoclonal gammopathy of undetermined significance (MGUS).

Patients and Methods: Fifty-eight patients with MM [age range, 34–87 years; stage I (n=11), stage II (n=12), stage III (n=35)], 31 patients with MGUS (age range, 43–85 years), and 185 healthy controls were included. The MM group consisted of 34 M-component type IgG, 12 IgA, 1 IgM, 9 Bence-Jones, and 2 non-secretory. Genotyping was determined by the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) technique. Genotype and allele frequencies were compared between the study groups by χ2 test. Odds ratios (OR) and 95% confidence intervals were calculated.

Results: The IL-10-592A/C genotype, which shows higher production of IL-10, was associated with an increased risk of MM (OR, 2.15; 95% confidence interval [95% CI], 1.17–3.93; P=0.012). The IL-10-592A/A genotype, which shows lower production of IL-10, was associated with a decreased risk of MM (OR 0.52; 95% CI, 0.27–1.00; P=0.047). Interestingly, 6 of 7 patients (86%) with transformation of MGUS to MM showed the IL-10-592A/C genotype. There was no association between the development of MGUS and the genotype of IL-10-592 polymorphism (Fig. 1). There was a trend to better overall survival of IL-10-592 A/A compared to IL-10-592 A/C or IL-10-592 C/C, although not significantly (Fig. 2). In addition, we noted that the ethnic distribution of IL-10-C592A was significantly different. The high producer IL-10-592 C/C genotype is present in only 10% of the Japanese population in our study compared to 35% of the Caucasian population in previous studies.

Conclusion: These results suggested that the IL-10-592 A/C genotype contributes to the susceptibility of MM development and prognosis in Japanese patients. Genetic variations of IL-10-592 polymorphism may also influence ethnic differences in myeloma incidence.

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Topics:
genotype, interleukin-10, multiple myeloma, promoter regions (genetics), monoclonal gammopathy of undetermined significance, polymerase chain reaction, bence jones protein, cytokine, genotype determination, immunoglobulin a

Disclosure: No relevant conflicts of interest to declare.

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2006, The American Society of Hematology
2006
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