Ethnicity Greatly Influences Cytokine Gene Polymorphism Distribution

Abstract

Polymorphisms in the regulatory regions of cytokine genes are associated with high and low cytokine production and may modulate the magnitude of alloimmune responses following transplantation. Ethnicity influences allograft half-life and the incidence of acute and chronic rejection. We have questioned whether ethnic-based differences in renal allograft survival could be due in part to inheritance of cytokine polymorphisms. To address that question, we studied the inheritance patterns for polymorphisms in several cytokine genes (IL-2, IL-6, IL-10, TNF-a, TGF-b, and IFNg) within an ethnically diverse study population comprised of 216 Whites, 58 Blacks, 25 Hispanics, and 31 Asians. Polymorphisms were determined by allele-specific polymerase chain reaction and restriction fragment length analysis. We found striking differences in the distribution of cytokine polymorphisms among ethnic populations. Specifically, significant differences existed between Blacks and both Whites and Asians in the distribution of the polymorphic alleles for IL-2. Blacks, Hispanics and Asians demonstrated marked differences in the inheritance of IL-6 alleles and IL-10 genotypes that result in high expression when compared with Whites. Those of Asian descent exhibited an increase in IFN-g genotypes that result in low expression as compared to Whites. In contrast, we did not find significant ethnic-based differences in the inheritance of polymorphic alleles for TNF-a. Our results show that the inheritance of certain cytokine gene polymorphisms is strongly associated with ethnicity. These differences may contribute to the apparent influence of ethnicity on allograft outcome.

The TNF−α –308, MCP−1 –2518 and TGF−β1 +915 polymorphisms are not associated with the development of chronic lung disease in very low birth weight infants

“…20,[28][29][30][31] The frequency of the À308 A allele is lower in those of African descent (10%). 31,32 Possible explanations for this observation are that the À308 A allele increases risk for preterm delivery, or increases need for MV at birth, or both. Indeed, preliminary reports suggest a role for this polymorphism in the etiology of preterm births.…”

IFNG polymorphisms are associated with gender differences in susceptibility to multiple sclerosis

“…51 Pravica et al 52 and others have shown that the I1(761)*CA 12 allele is associated with increased expression of IFNg mainly in homozygotes, although a trend toward increased expression was observed in heterozygotes, findings confirmed by others. [53][54][55] Pravica et al 56 also reported that an SNP in intron 1 [I1(759)*T-A] is in tight LD with I1(761)*CA n . The high-secretory I1(761)*CA 12 allele is in strong LD with I1(759)*T. Homozygosity for the I1(759)*A allele is associated with a 3.8-fold increase in risk of tuberculosis in Spain.…”

Cortisol and Cytokines in Chronic and Treatment-Resistant Patients with Schizophrenia: Association with Psychopathology and Response to Antipsychotics

“…Another possible explanation is that there are significant differences in IL-2 genotype frequencies observed in different populations. Recent studies have shown that inheritance of polymorphic cytokine gene alleles is dramatically influenced by ethnicity (Cox et al, 2001;Hoffmann et al, 2002). Moreover, a statistically significant ethnicity-based variability in the allelic frequency and genotype inheritance patterns for IL-2 and IL-6 has been reported (Cox et al, 2001), suggesting that polymorphisms within these cytokine genes may be responsible for the ethnic-based differences in IL-2 or IL-6 levels.…”