TY - JOUR
T1 - Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups
AU - Marron, Michele P.
AU - Raffel, Leslie J.
AU - Garchon, Henri Jean
AU - Jacob, Chaim O.
AU - Serrano-Rios, Manuel
AU - Martinez Larrad, Maria T.
AU - Teng, Wei Ping
AU - Park, Yongsoo
AU - Zhang, Zhi Xing
AU - Goldstein, Darlene R.
AU - Tao, Yi Wen
AU - Beaurain, Genevieve
AU - Bach, Jean Francois
AU - Huang, Hong So
AU - Luo, De Fang
AU - Zeidler, Adina
AU - Rotter, Jerome I.
AU - Yang, Mark C.K.
AU - Modilevsky, Tamara
AU - Maclaren, Noel K.
AU - She, Jin-Xiong
PY - 1997/8
Y1 - 1997/8
N2 - 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.
AB - 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.
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U2 - 10.1093/hmg/6.8.1275
DO - 10.1093/hmg/6.8.1275
M3 - Article
C2 - 9259273
AN - SCOPUS:8544274482
SN - 0964-6906
VL - 6
SP - 1275
EP - 1282
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 8
ER -