Genes for NIDDM in the HLA region on chromosome 6 - The Finland-
United States Investigation of NIDDM Genetics (FUSION). EVA
TUOMILEHTO-WOLF, GABI VIDGREN, STELLA NYLAND, WILLIAM A. HAGOPIAN,
TIMO VALLE, KIMMO KOHTAMAKI, MICHAEL BOEHNKE, FRANCIS S. COLLINS,
SOUMITRA GHOSH, JAAKKO TUOMILEHTO.

To reproduce and verify that genes in the HLA region (6p21.3)
play a role in conferring susceptibility not only to IDDM but
also to NIDDM 97 Finnish families with at least one pair of
siblings affected with NIDDM (ASP) were HLA genotyped by serology
(class I loci A,C,B and class II loci DR,DQ) as part of the
FUSION study. After careful clinical evaluation 11 families (11%)
were excluded as probable IDDM (treated with insulin within 3
years of diagnosis, GAD positive, low C-peptide and most had two
high risk IDDM associated HLA haplotypes). In the 86 NIDDM
families (age of onset 35-60 years) 33 (38%) of the affected
siblings shared two, 38 (44%) shared one and 15 (17%) shared no
HLA haplotype (p=0.01). These 15 (7 had a mother with NIDDM) were
found in families with only one ASP (total 66 families) where at
least two (till four) of the parental HLA haplotypes carried a
high risk for IDDM and had been seen as transmitted haplotypes
(TH) in a previous population-based Finnish IDDM study. 44%
(75/172) of the haplotypes seen in the 86 NIDDM probands were
such TH compared to 16% (201/1247) in the Finnish background
population (p<0.0001).

With this study we have confirmed that HLA genes play a
significant role in NIDDM.