Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups

Michele P. Marron, Leslie J. Raffel, Henri Jean Garchon, Chaim O. Jacob, Manuel Serrano-Rios, Maria T. Martinez Larrad, Wei Ping Teng, Yongsoo Park, Zhi Xing Zhang, Darlene R. Goldstein, Yi Wen Tao, Genevieve Beaurain, Jean Francois Bach, Hong So Huang, De Fang Luo, Adina Zeidler, Jerome I. Rotter, Mark C.K. Yang, Tamara Modilevsky, Noel K. MaclarenJin-Xiong She

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Abstract

Linkage disequilibrium (association) analysis was used to evaluate a candidate region near the CTLA4/CD28 genes using a multi-ethnic collection of families with one or more children affected by IDDM. In the data set unique to this study (Spanish, French, Mexican-American, Chinese and Korean), the transmission/disequilibrium test (TDT) revealed a highly significant deviation for transmission of alleles at the (AT)(n) microsatellite marker in the 3' untranslated region (P = 0.002) and the A/G polymorphism in the first exon (P = 0.00002) of the CTLA4 gene. The overall evidence for transmission deviation of the CTLA4 A/G alleles is also highly significant (P= 0.00005) in the combined data set (669 multiplex and 357 simplex families) from this study and a previous report on families from USA, Italy, UK, Spain and Sardinia. Significant heterogeneity was observed in these data sets. The British, Sardinian and Chinese data sets did not show any deviation for the A/G polymorphism, while the Caucasian-American data set showed a weak transmission deviation. Strong deviation for transmission was seen in the three Mediterranean-European populations (Italian, Spanish and French) (P = 10-5), the Mexican-American population (P = 0.002) and the Korean population (P = 0.03). These results suggest that a true IDDM susceptibility locus (designated IDDM12) is located near CTLA4.

Original languageEnglish (US)
Pages (from-to)1275-1282
Number of pages8
JournalHuman Molecular Genetics
Volume6
Issue number8
DOIs
StatePublished - Aug 1997
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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