Jenkinson C P, Hanson R, Cray K, Wiedrich C, Knowler W C, Bogardus C, Baier L
Phoenix Epidemiology and Clinical Research Branch, National Institute of Digestive Diabetes and Kidney Diseases, National Institutes of Health, Arizona, USA.
Int J Obes Relat Metab Disord. 2000 Oct;24(10):1233-8. doi: 10.1038/sj.ijo.0801381.
To investigate whether (a) variants within the dopamine D2 receptor gene (DRD2) are associated with obesity and type 2 diabetes in Pima Indians, and (b) whether variation in this gene could be responsible for previously observed linkage to these phenotypes, at chromosome location 11q23-24, in this population.
Two single nucleotide polymorphisms (SNPs), Ser311Cys and TaqIA, within the DRD2 gene were genotyped by allelic discrimination PCR in subjects who had provided evidence of linkage to diabetes and obesity in an autosome-wide scan.
A total of 1,187 subjects were genotyped, including 947 full heritage Pima Indians (80%). Descriptive statistics for all subjects analyzed, for whom clinical data were available, were (mean+/-s.d.): age at time of last exam = 41 +/- 15 y; birth year=1950 +/- 14; age-sex-adjusted body mass index (BMI; adjusted to a mean age of 35y)=36 +/- 8kg/m2; male = 44%; diabetic = 57%. For full heritage Pimas only: age = 43 +/- 15 y; birth year = 1948 +/- 14; sex- age-adjusted BMI = 36 +/- 8 kg/m2; male = 43%; diabetic = 59%.
Neither polymorphism was significantly associated with diabetes in full heritage Pimas. Individuals with a 'CG' genotype at the Ser311Cys SNP had a higher BMI than those with a 'CC' genotype (36.7 vs 35.5 kg/m2, P= 0.04). Linkage analysis of BMI, adjusted for either polymorphism, resulted in LOD scores that were similar to those obtained without adjustment.
Heterozygotes at the Ser311Cys DRD2 polymorphism had a slightly higher BMI than homozygotes, however neither the Ser311Cys nor the TaqIA polymorphism accounted for the linkage with BMI on chromosome 11 in Pima Indians.
(a) 研究多巴胺D2受体基因（DRD2）内的变异是否与皮马印第安人的肥胖症和2型糖尿病相关；(b) 该基因的变异是否可能是此前在该人群中观察到的、位于11号染色体q23 - 24区域与这些表型的连锁关系的原因。
通过等位基因鉴别PCR对DRD2基因内的两个单核苷酸多态性（SNP），即Ser311Cys和TaqIA进行基因分型，这些受试者在全基因组扫描中提供了与糖尿病和肥胖症连锁的证据。
共对1187名受试者进行了基因分型，其中包括947名纯血统皮马印第安人（80%）。对所有有临床数据的受试者进行的描述性统计为（均值±标准差）：末次检查时年龄 = 41±15岁；出生年份 = 1950±14；年龄性别校正体重指数（BMI；校正至平均年龄35岁）= 36±8kg/m²；男性 = 44%；糖尿病患者 = 57%。仅针对纯血统皮马人：年龄 = 43±15岁；出生年份 = 1948±14；性别年龄校正BMI = 36±8kg/m²；男性 = 43%；糖尿病患者 = 59%。
在纯血统皮马人中，这两种多态性均与糖尿病无显著关联。Ser311Cys SNP处具有“CG”基因型的个体比具有“CC”基因型的个体BMI更高（36.7对35.5kg/m²，P = 0.04）。对BMI进行连锁分析，无论是否对这两种多态性进行校正，得到的LOD值与未校正时相似。
Ser311Cys DRD2多态性的杂合子BMI略高于纯合子，然而Ser311Cys和TaqIA多态性均不能解释皮马印第安人11号染色体上与BMI的连锁关系。
