TY - JOUR
T1 - Meta-analysis of TNF-α promoter - 308 A/G polymorphism and SLE susceptibility
AU - Lee, Young H.
AU - Harley, John B.
AU - Nath, Swapan K.
N1 - Funding Information:
This work was supported by the National Institutes of Health (AR048928, AI063622, RR020143, AR049084, AI24717, AR42460, AR048940, AI053747, AR12253, DE15223, RR01577, RR14467) and the US Department of Veterans Affairs.
PY - 2006/3
Y1 - 2006/3
N2 - Alleles of tumor necrosis factor-Alleles of tumor necrosis factor-α (TNF-α) gene have been inconsistently associated with systemic lupus erythematosus (SLE), particularly the 308-A/G functional promoter polymorphism. To generate large-scale evidence on whether 308-A/G promoter polymorphism is associated with SLE susceptibility we have conducted a meta-analysis. We have identified 21 studies of this polymorphism and SLE using MEDLINE search. Meta-analysis was performed for genotypes A/A (recessive effect), A/A + A/G (dominant effect), and A allele in fixed or random effects models. All control samples were in Hardy-Weinberg proportion. The overall odds ratio (OR) of the A/A genotype was 3.2 (95% CI = 2.0-5.3, P<0.001). Stratification by ethnicity indicated that the A/A genotype was associated with SLE in European-derived population (OR = 4.0, CI = 2.5-6.4, P<0.001). No association was detected in Asian-derived population (OR, 1.3, CI = 0.3-6.3, P = 0.76). The overall OR for the risk genotypes (A/A and A/G) was 2.0 (CI = 1.3-3.1,P<0.001). Similar results were found between the risk allele A and SLE where a significant association was found in European population (OR = 2.1, CI = 1.6-2.7, Po0.001), but not in Asian (OR = 1.4, CI = 0.8-2.3, P = 0.2) or African (OR = 1.2, CI = 0.6-2.5, P = 0.59) populations. In summary, this meta-analysis demonstrates that the TNF-α promoter -308 A/G polymorphism may confer susceptibility to SLE, especially in European-derived population.
AB - Alleles of tumor necrosis factor-Alleles of tumor necrosis factor-α (TNF-α) gene have been inconsistently associated with systemic lupus erythematosus (SLE), particularly the 308-A/G functional promoter polymorphism. To generate large-scale evidence on whether 308-A/G promoter polymorphism is associated with SLE susceptibility we have conducted a meta-analysis. We have identified 21 studies of this polymorphism and SLE using MEDLINE search. Meta-analysis was performed for genotypes A/A (recessive effect), A/A + A/G (dominant effect), and A allele in fixed or random effects models. All control samples were in Hardy-Weinberg proportion. The overall odds ratio (OR) of the A/A genotype was 3.2 (95% CI = 2.0-5.3, P<0.001). Stratification by ethnicity indicated that the A/A genotype was associated with SLE in European-derived population (OR = 4.0, CI = 2.5-6.4, P<0.001). No association was detected in Asian-derived population (OR, 1.3, CI = 0.3-6.3, P = 0.76). The overall OR for the risk genotypes (A/A and A/G) was 2.0 (CI = 1.3-3.1,P<0.001). Similar results were found between the risk allele A and SLE where a significant association was found in European population (OR = 2.1, CI = 1.6-2.7, Po0.001), but not in Asian (OR = 1.4, CI = 0.8-2.3, P = 0.2) or African (OR = 1.2, CI = 0.6-2.5, P = 0.59) populations. In summary, this meta-analysis demonstrates that the TNF-α promoter -308 A/G polymorphism may confer susceptibility to SLE, especially in European-derived population.
KW - Meta-analysis
KW - SLE
KW - TNF-α
UR - http://www.scopus.com/inward/record.url?scp=33645159126&partnerID=8YFLogxK
U2 - 10.1038/sj.ejhg.5201566
DO - 10.1038/sj.ejhg.5201566
M3 - Article
C2 - 16418737
AN - SCOPUS:33645159126
VL - 14
SP - 364
EP - 371
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
SN - 1018-4813
IS - 3
ER -