Department of Clinical and Molecular Biochemistry, Pomeranian Medical University, ul. Powstancow Wlkp. 72, 70-111 Szczecin, Poland.
Pediatr Nephrol. 2013 Mar;28(3):433-8. doi: 10.1007/s00467-012-2277-7. Epub 2012 Aug 11.
A correlation between renal mass and nephron number in newborns allows the use of total kidney volume at birth as a surrogate for congenital nephron number. As the bone morphogenetic protein type 4 (BMP4), and its receptor type 1A (BMPR1A, ALK3), play an important role in renal development, we hypothesized that common, functional polymorphisms in their genes might be responsible for variation in kidney size among healthy individuals.
We recruited 179 healthy full-term newborns born to healthy women. Kidney volume was measured sonographically. Total kidney volume (TKV) was calculated as the sum of left and right kidneys, and normalized for body surface area (TKV/BSA). Genomic DNA was extracted from umbilical cord blood leukocytes, and c.455T > C (rs17563) BMP4 and c.67 + 5659A > T (rs7922846) BMPR1A genotypes were identified by PCR-RFLP.
TKV/BSA in newborns carrying at least one A BMPR1A allele (AA + AT) was significantly reduced by approximately 13 % as compared with TT homozygous newborns (106.7 ± 21.5 ml/m(2) vs. 122.7 ± 43.8 ml/m(2), p < 0.02). No significant differences in TKV/BSA were found among newborns with different BMP4 genotypes.
Results suggest that rs7922846 BMPR1A polymorphism may account for subtle variation in kidney size at birth, reflecting congenital nephron endowment.
新生儿肾质量与肾单位数量之间存在相关性，这使得出生时的总肾体积可作为先天性肾单位数量的替代指标。由于骨形态发生蛋白 4（BMP4）及其受体 1A（BMPR1A，ALK3）在肾脏发育中起着重要作用，我们假设它们基因中的常见功能多态性可能导致健康个体的肾脏大小存在差异。
我们招募了 179 名健康足月出生的健康产妇所生的新生儿。通过超声测量肾脏体积。左、右肾体积之和即为总肾体积（TKV），并通过体表面积（TKV/BSA）进行标准化。从脐血白细胞中提取基因组 DNA，采用 PCR-RFLP 法检测 c.455T > C（rs17563）BMP4 和 c.67 + 5659A > T（rs7922846）BMPR1A 基因型。
与 TT 纯合子新生儿（106.7 ± 21.5 ml/m2）相比，携带至少一个 A BMPR1A 等位基因（AA + AT）的新生儿 TKV/BSA 显著降低约 13%（122.7 ± 43.8 ml/m2，p < 0.02）。不同 BMP4 基因型新生儿的 TKV/BSA 无显著差异。
结果表明，rs7922846 BMPR1A 多态性可能导致出生时肾脏大小的细微差异，反映了先天性肾单位的数量。
