限局性糸球体硬化症の遺伝子マーカー

The study population includes several distinct populations of FSGS patients and healthy controls: patients of African descent, patients of Tamilian descent, healthy participants of African, European, Asian, and Tamilian descent, as well as people of African descent with HIV but without FSGS and adults who donate kidneys at NIH. The purpose of collecting samples for genetic analyses from these groups is to discover genetic variations that could be associated with FSGS, which is especially prevalent in African-American and Tamil populations.

• INCLUSION AND EXCLUSION CRITERIA, BY GROUP:

  1. African-descent with FSGS: renal biopsy showing FSGS or collapsing glomerulopathy, including HIV-associated collapsing glomerulopathy (HIV-associated nephropathy). We will include adult and pediatric patients. We will exclude patients with hyperfiltration FSGS.
  2. Other patients with FSGS (similar inclusion and exclusion criteria as in group 1).
  3. African descent with HIV and without kidney disease (controls). We will include adult patients who have had serologically confirmed HIV-1 infection for at least 8 years and lack clinical renal disease, as evidenced by normal creatinine and urine protein/creatinine ratio <0.5 or 24 hour urine protein excretion <500 mg/d.
  4. African descent (controls). We will include adults only. Exclusions will include HIV-1 infection, cardiovascular disease, and renal disease.
  5. European and Asian descent (controls). These samples represent DNA already obtained by Dr. Winkler s group under IRB approved protocols and these patients will not be recruited as part of the present study.<TAB>
  6. Relatives of patients with FSGS. In selected families (in which a patient has been found to have a mutation in an FSGS risk gene whose pathologic role has not been established), we will obtain individual histories of renal disease (hematuria, proteinuria, hypertension, nephrolithiasis) and will measure serum creatinine and urine protein excretion. We will include adults with and without renal disease and children with renal disease. We will evaluate children <18 years by obtaining a urine sample; if urinalysis and urine protein excretion are normal, we will not request a blood sample unless blood is being obtained for a clinical indication.
  7. Kidney donors. We will include NIH kidney donors only. We will obtain individual histories that provide information as to age, sex, race, surgical and medical histories, and family history. Our purpose is to examine whether particular genetic variants, including those in MYH9, influence the ability of the kidney to undergo hypertrophy following renal donation or the propensity to manifest albuminuria as a sign of glomerular stress. These findings have the potential to extend our understanding of the biology of MYH9 and might have clinical relevance for selecting kidney donors.
  8. Tamil population. We will recruit from a Tamil population. A Tamil will be defined as anyone that identifies themselves, their parents and their grandparents as Tamilian. We will ask these patients about their family history. We will exclude subjects under 18 and multiple subjects within the same family. We will draw blood for genetic testing. Our purpose is to determine whether particular genetic variants, including those in MYH9, are prevalent in a Tamilian population. If prevalence is indicated, we hope to study how these variants influence the progression of kidney disease in this population.
  9. Women who are pregnant will be excluded from participating in the apheresis component of this protocol.