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OBJECTIVE: Family-based association analysis was performed to investigate whether the angiotensin-converting enzyme (ACE)-G261T and ACE-A592G polymorphisms are risk factors for systemic lupus erythematosus (SLE) in a Chinese population. METHODS: A total of 119 patients with SLE from 95 nuclear families, aged from 14 to 78 years, who met the American College of Rheumatology 1997 criteria, were recruited, as were 316 family members of these patients. A family-based association study was used to explore the association between ACE gene polymorphisms (ACE-G261T and ACE-A592G) and SLE. The ACE gene polymorphisms were genotyped with restriction fragment length polymorphism-polymerase chain reaction. RESULTS: Using family-based association tests, the T allele of the ACE-G261T single-nucleotide polymorphism (SNP) was significantly associated with genetic susceptibility to SLE in an additive model (Z = 2.877, p = 0.004), a dominant model (Z = 2.557, p = 0.011), and a recessive model (Z = 2.202, p = 0.028). No association between the ACE-A592G SNP and SLE susceptibility was determined. CONCLUSION: The T allele of the ACE-G261T SNP was associated with SLE in this Chinese population.