Possible association between CTLA4 DNA polymorphisms and early onset type 1 diabetes in a UK population

Abstract

Linkage and association has been reported between CTLA4 DNA markers and susceptibility to type 1 diabetes in some populations, but not others. We performed case-control and family-based association studies to assess if the CTLA4 A49G and intron 1 C/T polymorphisms were associated with development of early onset type 1 diabetes in the Northern Ireland population. The distribution of A49G and C/T alleles in cases (n = 144) was similar to those observed in controls (n = 307). In contrast, significant distortions in allele transmissions from informative parents to probands were observed for both the A49G (P = 0.02) and C/T (P = 0.01) polymorphisms employing 297 nuclear families. Our results suggest that the CTLA4 gene may play a minor role in the overall genetic predisposition to type 1 diabetes in this UK population.

Genetics of type 1 diabetes mellitus

“…170 There is a microsatellite marker in the 3ЈUTR of the CTLA4 sequence, and several polymorphisms have been detected at CTLA4. 39 These polymorphisms, in particular the exon 1 (49 GϾA) SNP, have been investigated by TDT analysis in several populations, 41,140,[171][172][173][174][175][176][177][178][179][180][181][182][183][184][185][186] and combined data sets from these large studies support linkage of the CTLA4 locus to T1D. 168,171,187 Interestingly, some evidence has also been produced to suggest that CTLA4 polymorphisms may influence gene expression.…”

The CTLA4 + 49A/G and CT60 polymorphisms and chronic inflammatory arthropathies in Northern Ireland

“…while the second set of controls included 307 unrelated healthy children aged 12 to 15 who were selected from a random sample of Northern Ireland schools (McCormack et al, 2001). All patients were assessed by a rheumatologist and fulfilled the American College of Rheumatology criteria for RA (Arnett et al, 1988;Petty et al, 1998;Wood, 1978).…”

Association of CTLA-4 Polymorphisms with Type 1 Diabetes in the Egyptian Population

“…Apart from re-sequencing, association of CTLA-4 variants in different populations is a strategy for further fine mapping. In general, the compelling data on the association of CTLA-4 polymorphisms with T1D is convincing in some populations including Belgian [4,9], French, Italian, Korean, Mexican, Spanish-American [10], Japanese [11][12][13][14][15], Chinese [16], Russian [17], British [18], Moroccan [19], Estonian [20], and Croatian [21] populations.…”