Sepehrnia B, Prezant T R, Rotter J I, Pettitt D J, Knowler W C, Fischel-Ghodsian N
Ahmanson Department of Pediatrics, Steven Spielberg Pediatric Research Center, Los Angeles, California, USA.
Am J Med Genet. 1995 Mar 27;56(2):198-202. doi: 10.1002/ajmg.1320560217.
More than half of the Pima Indians over age 35 years have non-insulin-dependent (type II) diabetes mellitus (NIDDM). Extensive data indicate the importance of maternal diabetes in determining their risk for diabetes. Generally, the risk of having NIDDM is higher in patients with affected mothers than affected fathers. This has been attributed to intrauterine factors, but recently mitochondrial inheritance has been raised as an alternative hypothesis. In other populations, several families and individuals with diabetes due to a mitochondrial DNA point mutation at nucleotide 3243 in the tRNA(leu(UUR)) gene have been described, as has one family with a 10.4 kb mitochondrial DNA duplication/deletion. We tested whether these specific mitochondrial gene mutations could explain a portion of the excess maternal transmission seen in the Pima Indians. Mitochondrial DNA obtained from blood lymphocytes of 148 Pima Indians with NIDDM was screened both for the point mutation at nt 3243, and the 10.4 kb duplication/deletion. Neither of these mutations was detected, and although a small proportion of the excess maternal transmission in Pima Indians could still be due to yet undescribed mitochondrial mutations or imprinted nuclear genes, our data support the role of the intrauterine environment in this population.
超过半数的35岁以上皮马印第安人患有非胰岛素依赖型（II型）糖尿病（NIDDM）。大量数据表明，母亲患糖尿病对其子女患糖尿病风险的影响重大。一般来说，母亲患NIDDM的患者比父亲患NIDDM的患者发病风险更高。这一直被归因于子宫内因素，但最近线粒体遗传作为一种替代假说来被提及。在其他人群中，已经描述了几个因线粒体DNA在tRNA(leu(UUR))基因的3243位核苷酸处发生点突变而患糖尿病的家族和个体，还有一个家族存在10.4 kb线粒体DNA重复/缺失。我们测试了这些特定的线粒体基因突变是否可以解释皮马印第安人母亲遗传糖尿病风险过高现象的一部分原因。对148名患NIDDM的皮马印第安人的血液淋巴细胞中的线粒体DNA进行了筛查，检测其是否存在3243位核苷酸的点突变以及10.4 kb的重复/缺失。这两种突变均未检测到，虽然皮马印第安人母亲遗传糖尿病风险过高现象中的一小部分仍可能归因于尚未被描述的线粒体突变或印记核基因，但我们的数据支持子宫内环境在该人群中的作用。
