Xiang K, Zheng T, Lu H
Department of Endocrinology, Shanghai 6th People Hospital.
Zhonghua Yi Xue Za Zhi. 1998 Nov;78(11):817-20.
To ascertain the presence of the Ser 20Gly mutation of islet amyloid polypeptide (IAPP) gene and its impact on NIDDM in Chinese.
In 896 Chinese, 825 were unrelated subjects (NIDDM in 609 and non-diabetics, 216) and 71 were family members of the pedigrees with IAPP gene-Ser 20Gly carrier probands detected from population screening. The mutation was examined by PCR-RFLP MspI digestion in population screening and the results was randomly checked by direct DNA sequencing. Data were analyzed through association as well as linkage approaches.
The Ser20Gly mutation of the IAPP gene was observed in Chinese. It was more prevalent in NIDDM (17 cases, 2.8%) than in non-diabetics (1 cases, 0.5%) (Fisher two-tailed exact P = 0.05). The mutation carrier detected by PCR-RFLP was confirmed to be the A to G point mutation in nucleotide 582 of IAPP gene cDNA encoding the amino acid codon 20. All the mutation carriers detected in population screening were heterozygotes. Analysis of the family members of the 12 NIDDM pedigrees with the IAPP gene Ser20Gly mutation showed that in two families, the mutation was not cosegregated with the affection status. The older was the age of Ser20Gly mutant carrier, the more prevalent was the diabetes in families (P = 0.0001). The highest total lod score of this 12 pedigree was 0.021(theta = 0) in parametric linkage analysis with the model of autosomal dominance with incomplete penetrance.
The Ser20Gly mutation of IAPP gene was present in Chinese. This mutation does not cause monogenic inheritance diabetes, but may be a pathogenetic factor for the development of NIDDM, the complex genetic disease.
确定胰岛淀粉样多肽（IAPP）基因Ser 20Gly突变在中国人群中的存在情况及其对非胰岛素依赖型糖尿病（NIDDM）的影响。
选取896名中国人，其中825名是无关个体（609名NIDDM患者和216名非糖尿病患者），71名是通过人群筛查检测到的携带IAPP基因Ser 20Gly突变的先证者的家系成员。在人群筛查中通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）MspI酶切检测该突变，并通过直接DNA测序随机检查结果。通过关联分析和连锁分析方法对数据进行分析。
在中国人群中观察到IAPP基因的Ser20Gly突变。该突变在NIDDM患者中（17例，2.8%）比在非糖尿病患者中（1例，0.5%）更常见（Fisher双尾精确P = 0.05）。通过PCR-RFLP检测到的突变携带者被确认为IAPP基因cDNA编码氨基酸密码子20的第582位核苷酸由A到G的点突变。在人群筛查中检测到的所有突变携带者均为杂合子。对12个携带IAPP基因Ser20Gly突变的NIDDM家系的家系成员分析表明，在两个家系中，该突变与患病状态不共分离。Ser20Gly突变携带者年龄越大，家族中糖尿病的患病率越高（P = 0.0001）。在常染色体显性遗传且外显不全模型的参数连锁分析中，这12个家系的最高对数优势总分是0.021（θ = 0）。
IAPP基因的Ser20Gly突变存在于中国人群中。该突变不会导致单基因遗传性糖尿病，但可能是复杂遗传性疾病NIDDM发病的一个致病因素。
