Exclusion of adenosine deaminase gene locus on chromosome 20q12–13.1 in familial NIDDM in Taiwanese patients

Diabetologia, Dec 1995

Dr. B. J. Lin

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

https://link.springer.com/content/pdf/10.1007%2FBF00400617.pdf

Exclusion of adenosine deaminase gene locus on chromosome 20q12–13.1 in familial NIDDM in Taiwanese patients

Exclusion of adenosine deaminase gene locus on chromosome 20q12-13.1 in familial NIDDM in Taiwanese patients Yours sincerely 0 L.-M. Chuang 0 K. C. Chiu 0 H.-R Wu 0 T.-S. Jou 0 T.-Y. Tai 0 B. J. Lin 0 0 Sincerely yours , M. Songini 4. Chomyn A, Martinuzzi A, Yoneda M e t al. (1992) M E L A S mutation in m t D N A binding site for transcription termination factor causes defects in protein synthesis and in respiration but no change in levels of upstream and downstream mature transcripts. Proc Natl A c a d Sci U S A 89:4221-4225 5. Yoneda M, Chomyn A, Martinuzzi A, Hurko O, Attardi G (1992) Marked replicative advantage of human m t D N A carrying a point mutation that causes the M E L A S encephalomyopathy. Proc Natl A c a d Sci U S A 89:11164-11168 6. King MR Koga Y, Davidson M, Schon E A (1992) Defects in mitochondrial protein synthesis and respiratory chain activity segregate with the t R N A cEU(uUR) mutation associated with MELAS. Mol Cell Biol 12:480-490 I: Frequency of disease gene: 0.0001 100 % Age-dependent" 100 % Age-dependenta II: Frequency of disease gene: 0.01 100 % Age-dependenta 100 % Age-dependent~ a Age-dependent penetrance as described previously [2] IGT, Impaired glucose tolerance Dear Sir, The linkage between adenosine deaminase gene locus on chromosome 20q12-13.1 and maturity-onset diabetes of the young (MODY, a subset of non-insulin-dependent diabetes mellitus [ N I D D M ] ) was found in the R - W pedigree [ 1, 2 ]. Furthermore, defective beta-cell function has been demonstrated in the non-diabetic members of the R - W pedigree who had inherited the disease allele [ 3 ]. Those who inherited the disease allele at this locus may be predisposed to N I D D M ; thus, this locus is a candidate gene locus for N I D D M . By parametric methods, adenosine deaminase locus was excluded as a c a u s e of MODY in Edinburgh (UK), Wisconsin (USA) and French pedigrees [ 2, 4 ] and by non-parametric methods, no linkage was found between the adenosine deaminase locus and N I D D M in 50 diabetic sib sets from the United Kingdom and Italy [ 5 ]. However, its role in the pathogenesis of familial N I D D M in the Asian population has not been examined. We studied this locus in 213 subjects from 17 multiplex Taiwanese pedigrees with N I D D M with both L I N K A G E (version 5.1) and affected-pedigree-member (APM) method (version 2.0) software programs. In order to reduce the risk of missing a true linkage, linkage analysis was performed under four diagnostic schemes, based on the World Health Organization diagnostic criteria for diabetes with either high or low frequency of the disease gene. As shown in Figure 1, the linkage was rejected by the summed log of the odds (LOD) scores in most of the cases under an autosomal dominant model. Since N I D D M is a heterogenous disease, the A-test for heterogeneity among the studied pedigrees was tested based on the results of two-point linkage analyses by using the H O M O G (version 3.33) program of L I N K A G E computer software package. No apparent heterogeneity was noted within the studied pedigree. Only one studied pedigree met the criteria for MODY (age at diagnosis ranging from 21 to 27 years) and linkage was also excluded in this pedigree. Linkage analysis by the A P M method provides another means to analyse a complex trait such as N I D D M without prior assumption of the mode of inheritance, since the mode of inheritance is unknown. However, the A P M method is much more dependent on the allelic frequency; the allelic fre Penetrance Diagnostic scheme a Overt diabetes, IGT vs unaffected Overt diabetes, IGT vs unaffected Overt diabetes vs unaffected Overt diabetes, IGT vs unaffected Overt diabetes, IGT vs unaffected Overt diabetes vs unknown Overt diabetes, IGT vs unaffected Overt diabetes, IGT vs unaffected Overt diabetes vs unaffected Overt diabetes, IGT vs unaffected Overt diabetes, IGT vs unaffected Overt diabetes vs unknown Summed LOD score --oa -28.46 -20.52 -20.78 - 9.06 -30.14 - 7.47 -23.21 - 6.46 - 3.19 - 0.48 quency in Taiwanese patients was estimated from 64 unrelated non-diabetic Taiwanese subjects. No linkage was found under two diagnostic schemes by defining overt diabetes as affected or by defining both overt diabetes and impaired glucose tolerance as affected. In conclusion, studies of the adenosine deaminase locus on chromosome 20q12-13.1 in the Taiwanese population indicate that this locus does not play a major role in familial N I D D M in this population and this observation agrees with the negative results in 50 European sib sets [ 5 ]. However, these data do not exclude a minor effect in the Taiwanese population. The latter issue can only be addressed directly after cloning of the responsible gene and identification of the mutation in the R-W pedigree. Incidence of IDDM in southern Europe Dear Sir, Recently, in a very interesting paper, Roglic et al. [ 1 ] reported the incidence of insulin-dependent diabetes mellitus (IDDM) in Zagreb, Croatia. The prospective study, which took place during 1988-1992, using the capture-recapture method, showed an annual incidence rate over the 5-year period ranging from 5.6 to 6.6/100,000. The incidence peaked in the 1014 year age group (12.4/100,000) while it remained stable over 24 years of age. The rates in the 15-30 years age group were close to 8/100,000. The authors concluded that: 1) childhood incidence of I D D M in Zagreb appears to be low and is similar to that of both southern European populations and those Of Slavic origin; 2) the peak, occurring in the 10-14 year age group, has also been reported for many other populations with very different rates; 3) rates for the 15-30 year age group were close to those found in some Italian areas (Turin and its province and Lombardy). Regretfully, the authors did not consider a previous study carried out in Italy (Sardinia) by our group, using essentially the same approach, which was the first standardised study to demonstrate that the incidence of I D D M in Sardinia was much higher than expected in a southern European region. During 1989-1990 [ 2 ] we were able to show in Sardinia (ascertainment probability of 92.8 %) a standardised incidence rate for people aged 0-29 years of 24.3/100,000 (0-14 years: 30/100,000; 15-29 years: 18.7/100,000) with a plateau of incidence rate at 5-14 years (5-9 years: 32.0/100,000 and 1014 years: 32.8/100,000). Male/female ratios in the 0-29 and 0-14 years age groups were 1.55 and 1.25, respectively, with the highest ratio, 3.38, in the 25-29 year age group and the lowest, 1~14, in the 0-4 years group. Therefore, these data, coming from an area at a very high risk for IDDM, confirm the earlier peaking of I D D M also described in the four Italian regions included in the E U R O D I A B A C E network [ 3 ] References plus Liguria [ 4 ] and Piedmont [ 5 ]. In Estonia [6] the highest incidence rate is registered in the 15-19 year age group, despite the fact that puberty in this country starts earlier than in Italy (at age 10 years for females and 12 years for males). A male/female ratio greater than 1 has also been confirmed and described in other nations such as the United Kingdom [7], Luxembourg [8], France [9], Norway [10] and Finland [11]. E U R O D I A B A C E data confirm this trend particularly in areas with high incidence rates such as Finland, Sardinia and Norway; the opposite trend on the other hand is observed in certain areas with low incidence rates such as Israel, Poland and Rumania [ 2 ]. Recent data collected by some E U R O D I A B A C E centres extending their age range up to 29 years have shown a pronounced excess of males but only for populations with medium or high background risk levels. Sex trends resulting from the E U R O D I A B A C E data concerning childhood I D D M seem to be more pronounced at higher age levels; this is one of the reasons why the E U R O D I A B A C E steering committee decided to set up a new multicentre European substudy on I D D M with onset in young adulthood (15-29 years) whose main aim is to better define the traditionally "heterogeneous" group of late-onset I D D M patients. References 1. Bell GI , Xiang KS , Newman M V e t al . ( 1991 ) Gene for noninsulin-dependent diabetes mellitus (maturity-onset diabetes of the young subtype) is linked to D N A polymorphism on human chromosome 20 q . Proc Natl Acad Sci U S A 88 : 1484 - 1488 2. Bowden DW , Akots G , Rothschild CB et al. ( 1992 ) Linkage analysis of maturity-onset diabetes of the young (MODY): genetic heterogeneity and nonpenetrance . A m J Hum Genet 50 : 607 - 618 3. Herman WH , Faj ans SS , Ortiz FJ et al. ( 1994 ) Abnormal insulin secretion, not insulin resistance, is the genetic or primary defect of M O D Y i n the RW pedigree . Diabetes 43 : 40 - 46 4. Vaxillaire M , Vionnet N , Vigouroux C et al. ( 1994 ) Search for a third suceptibility gene for maturity-onset diabetes of the young . Studies with eleven candidate genes . Diabetes 43 : 389 - 395 5. Baroni MG , Alcolado JC , Needham EW , Pozzilli P , Stockes J , Galton DJ ( 1992 ) Sib-pair analysis of adenosine deaminase locus in NIDDM . Diabetes 41 : 1640 - 1643 1. Roglic G , Pavlic-Renar I , Sestan- Crnek S e t al. ( 1995 ) Incidence of I D D M during 1988 -1992 in Zagreb, Croatia. Diabetologia 38 : 550 - 554 2. Muntoni S , Songini M and the Sardinian Collaborative Group for Epidemiology of I D D M in Sardinia (1992) High incidence rate of I D D M in Sardinia . Diabetes Care 15 : 1317 - 1322 3. Green A , Gale EAM , Patterson CC for the E U R O D I A B A C E Study Group ( 1992 ) Incidence of childhood-onset insulin-dependent diabetes mellitus: the E U R O D I A B A C E Study . Lancet 339 : 905 - 909


This is a preview of a remote PDF: https://link.springer.com/content/pdf/10.1007%2FBF00400617.pdf

Dr. B. J. Lin. Exclusion of adenosine deaminase gene locus on chromosome 20q12–13.1 in familial NIDDM in Taiwanese patients, Diabetologia, 1995, 1490-1491, DOI: 10.1007/BF00400617