Variation outside of the range of the TRPM8 receptor affects multiple sclerosis prevalence rates
 
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Ohio State University Alumni Association, Columbus, OH, USA
CORRESPONDING AUTHOR
Ernest Lad Heisten IV   

3669 Dragonfly Dr., Columbus Ohio, 43204 United States. Tel.: +1614 260-0125.
Online publish date: 2018-06-18
Publish date: 2019-10-31
Submission date: 2017-05-28
Acceptance date: 2017-07-10
 
Pol. Ann. Med. 2019;26(1):14–19
ABSTRACT
Introduction:
TRPM8 is an immune system regulator with a peak activity at 8°C–10°C. Multiple sclerosis (MS) is a condition that is noted for an increasing prevalence with latitude. Prevalence rates have, however, been noted to drop in northern regions with averages yearly temperatures below 8°C

Aim:
To determine whether MS prevalence rates are associated with the peak of TRPM8 activity of 8°C–10°C both by average yearly temperature and by variation towards that temperature.

Material and methods:
Multivariate analysis was used to determine the significance of association between MS prevalence, average yearly temperature, and with variation towards a particular temperature. This method was repeated for eight independent regions, all regions combined, and all regions except Russia and Scandinavia.

Results and discussion:
Results showed an average yearly temperature for peak MS prevalence between 6.00°C and 10.80°C depending on region. The average temperature for peak effects of variation was between 7.80°C and 8.70°C depending on region, with the UK and Scandinavia non-significant. The average temperature of association with MS for all regions was 9.21° by temperature (P < 0.05) and by variation 8.67°C (P < 0.005). Without Russia and Scandinavia the average temperature was 10.55°C (P < 0.05) and variation was not significant.

Conclusions:
Removing northern regions from the model causes variation to become non-significant by removing areas where, on average, variation towards warmer temperatures increase MS rates instead of variation towards lower ones. This provides evidence that average yearly temperature and variation from that temperature are responsible for significant variations in MS prevalence rates worldwide.

ACKNOWLEDGEMENTS
This research was conducted independently and not on behalf of the Ohio State Alumni Association. No conflict of interest exists in this relationship.
CONFLICT OF INTEREST
Author declare to have no conflict of interest.
 
REFERENCES (69)
1.
Heisten, E. Peak TRPM8 Activity is Associated with MS Prevalence. Human Physiology/Fiziologiia Cheloveka Journal [in print; in Russian].
 
2.
Bautista DM, Siemens J, Glazer JM, et al. The menthol receptor TRPM8 is the principal detector of environmental cold. Nature. 2007;448(7150):204–208. https://doi.org/10.1038/nature....
 
3.
Rosati G. The Prevalence of multiple sclerosis in the world: an update. Neurol Sci. 2001;22(2):117–139. https://doi.org/10.1007/s10072....
 
4.
Norwegian Meteorlogical Institute. Average Yearly Temperature for all locations tested. https://www.yr.no/?spr=eng. Accessed June 5, 2018.
 
5.
Boyko A, Smirnova N, Petrov S, Gusev E. Epidemiology of MS in Russia, a historical review. Mult Scler Demyelinating Disord. 2016;1:13. https://doi.org/10.1186/s40893....
 
6.
Larsen JP, Riise T, Nyland H, Kvale G, Aarli JA. Clustering of multiple sclerosis in the county of Hordaland, Western Norway. Acta Neurol Scand. 1985;71(5):390–395. https://doi.org/10.1111/j.1600....
 
7.
Celius EG. Multiple sclerosis in Oslo, Norway. Mult Scler. 1998;4:367.
 
8.
Gronning M, Mellgren SI. Multiple sclerosis in the two northernmost counties of Norway. Acta Neurol Scand. 1985;72(3):321–327. https://doi.org/10.1111/j.1600....
 
9.
Svenningsson A, Runmarker B, Lycke J, Andersen O. Incidence of multiple sclerosis during two fifteen-year periods in the Gothenburg region of Sweden. Acta Neurol Scand. 1990;82(3):161–168. https://doi.org/10.1111/j.1600....
 
10.
Koch-Henriksen N. The Danish multiple sclerosis registry: a 50-year follow-up. Mult Scler. 1999;5(4):293–296. https://doi.org/10.1177/135245....
 
11.
Wikstrom J, Tienari PJ, Sumelahti ML, Hovi E. Multiple sclerosis in Finland: evidence of uneven geographic distribution, increasing frequency and high familial occurrence. In: Firnhaber W, Lauer K, eds. Multiple Sclerosis in Europe: An Epidemiological Update. Darmstadt: Leuchtturm-Verlag. 1994;73–78.
 
12.
Benedikz JEG, Magnusson H, Poser CM, Gudmundsson G. Multiple sclerosis in Iceland 1 January 1900 – 31 December 1989: a 90 year total population study. Ann Neurol. 1994;36(Suppl 2):175–179. https://doi.org/10.1002/ana.41....
 
13.
Kurtzke, JF. A Reassessment of the distribution of multiple sclerosis. Part one. Acta Neurol Scandinav. 1975;51(2):110–136. https://doi.org/10.1111/j.1600....
 
14.
Taylor B, Richardson A, Mason D, et al. Prevalence of Multiple Sclerosis in New Zealand. University of Otago. Multiple Sclerosis study group. https://www.msnz.org.nz/wp-con.... Accessed June 5, 2018.
 
15.
Vukusic S, Bockstael VV, Gosselin S, Confavreux C. Regional variations in the prevalence of multiple sclerosis in French farmers. J Neurol Neurosurg Psychiatry. 2007;78(7):707–709. https://doi.org/10.1136/jnnp.2....
 
16.
Dean G, Grimaldi G, Kelly R, Karhausen L. Multiple sclerosis in southern Europe. I. Prevalence in Sicily in 1975. J Epidemiol Community Health. 1979:33:107–110. https://doi.org/10.1136/jech.3....
 
17.
Savettieri G, Elian M, Giordano D, Grimaldi G, Ventura A, Dean G. A further study on the prevalence of multiple sclerosis in Sicily: Caltanissetta city. Acta Neurol Scand. 1986;73:71–75. https://doi.org/10.1111/j.1600....
 
18.
Savettieri G, Salemi G, Ragonese P, Aridon P, Scola G, Randisi G. Prevalence and incidence of multiple sclerosis in Monreale city, Italy. J Neurol. 1998;245(1):40–43. https://doi.org/10.1007/s00415....
 
19.
Salemi G, Ragonese P, Aridon P, et al. Multiple sclerosis in Southern Europe: incidence and prevalence in Bagheria City, Sicily, Italy. Neuroepidemiology. 1998;17:218.
 
20.
Nicoletti A, Bartolo ML, Fermo S, et al. Prevalence and incidence of multiple sclerosis in Catania, Sicily. Neuroepidemiology. 2000;19:160.
 
21.
Iuliano G, Napoletano R. Prevalence and incidence of multiple sclerosis in Salerno (southern Italy) and its province. Eur J Neurol. 2008:15(1):73–76.
 
22.
Maddestra M, Sabbatini S, Paci F, Paci A. Epidemiological survey of multiple sclerosis in the province of Terni. Neuroepidemiology. 1998;17:54.
 
23.
Angeleri F, Bollettini G, Brizioli E. prevalence study of multiple sclerosis in the Regione Marche. In: Battaglia MA, Crimi G, eds. An update on multiple sclerosis. Bologna: Monduzzi. 1989:209–212.
 
24.
Totaro R, Marini C, Cialfi A Giunta M, Carolei A. Prevalence of multiple sclerosis in the L’Aquila district, central Italy. J Neurol Neurosurg Psychiatry. 2000;68(3):349–352. https://doi.org/10.1136/jnnp.6....
 
25.
Granieri E, Malagú S, Casetta I Tola MR, Govoni V, Paolino E, Monetti VC. Multiple sclerosis in Italy. A reappraisal of incidence and prevalence in Ferrara. Arch Neurol. 1996;53(8):793–798. https://doi.org/10.1001/archne....
 
26.
Meucci G, Bianchi F, Rossi G. Indagine sulla prevalenza della sclerosi multipla nella USL n.17 del Valdarno inferiore. In: 7th Italian Congress of Neuroepidemiology. Abstract Book. Perugia: Tipografia Umbra Perugia. 1992;17:35.
 
27.
Granieri E, Casetta I, Govoni V, et al. The increasing incidence and prevalence of MS in a Sardinian province. Neurology. 2000;55(6):842–847. https://doi.org/10.1212/WNL.55....
 
28.
Pugliatti M, Sotgiu S, Solinas G, et al. Multiple sclerosis epidemiology in Sardinia: evidence for a true increasing risk. Acta Neurol Scand. 2001;103(1):20–26. https://doi.org/10.1034/j.1600....
 
29.
Sironi L, Mamoli A, D’Alessandro G, Corso G, Bottachi E. Epidemiology of multiple sclerosis in Valle D’Aosta, Italy. Mult Scler. 1997;3:283.
 
30.
Bergamaschi R, Montomoli C, Candeloro E, et al. Bayesian mapping of multiple sclerosis prevalence in the province of Pavia, northern Italy. J Neurol Sci. 2006;244(1–2):127–131. https://doi.org/10.1016/j.jns.....
 
31.
Gajofattoa A, Stefania A, Turattia M, et al. Prevalence of multiple sclerosis in Verona, Italy: an epidemiological and genetic study. Eur J Neurol. 2013;20(4):697–703. https://doi.org/10.1111/ene.12....
 
32.
Millefiorini E, Cortese A, Rezze SD, et al. The prevalence of multiple sclerosis in central Italy. Mult Scler. 2010;16(12):1432–1436. https://doi.org/10.1177/135245....
 
33.
Bellantonioa P, Iulianob G, Di Blasioa F, Ruggieria S. Prevalence and incidence of multiple sclerosis in Campobasso (Molise region chieftown, southern Italy). Clin Neurol Neurosurg. 2013;115:1806–1808. https://doi.org/10.1016/j.clin....
 
34.
Grimaldi LE, Palmeri B, Salemi G, et al. High prevalence and fast rising incidence of multiple sclerosis in Caltanissetta, Sicily, Southern Italy. Neuroepidemiology. 2007;28(1):28–32. https://doi.org/10.1159/000097....
 
35.
Savettieri G, Salemi G, Ragonese P, Aridon P, Scola G, Randisi G. Prevalence and incidence of multiple sclerosis in the city of Monreale, Italy. J Neurol. 1998;245(1):40–43. https://doi.org/10.1007/s00415....
 
36.
Sironi L, Mamoli A, D’Alessandro G, Camerlingo M, Bottachi E. Frequency of multiple sclerosis in Valle D’Aosta, 1971–1985. Neuroepidemiology. 1991;10(2):66–69. https://doi.org/10.1159/000110....
 
37.
Moresco M, Rossi G. Studio di prevalenza della sclerosi multipla nella USL Vallagarina-Rovereto. In: Battaglia MA, Crimi G, eds. An Update on Multiple Sclerosis. Bologna: Monduzzi. 1989;287–291.
 
38.
Diodato S, Cattaino G, Lisotto C, Pomes A. Multiple sclerosis epidemiological survey in Pordenone. In: Battaglia MA, Crimi G, eds. An Update on Multiple Sclerosis. Bologna: Monduzzi. 1989:231-233.
 
39.
Nardozza V, Chiò A, Santoni M, Marforio S. Prevalence of multiple sclerosis in the town of Biella, northern Italy. In: An update on multiple sclerosis, Scientific Meeting sponsored by IFMSS-ECTRIMS, Rome, 14-17 September 1998. Abstract Book. Rome: AISM. 1998;4:37.
 
40.
Rosati G. Descriptive epidemiology of multiple sclerosis in Europe in the 1980s: A critical overview. Ann Neurol. 1994:36(Suppl 2):S164–S174. https://doi.org/10.1002/ana.41....
 
41.
Sadovnick AD, Ebers GC. Epidemiology of multiple sclerosis: A critical overview. Can J Neurol Sci. 1993;20(1):17–29. https://doi.org/10.1017/S03171....
 
42.
Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med. 2000:343(13):938–952. https://doi.org/10.1056/NEJM20....
 
43.
Phadke JG, Downie AW. Epidemiology of multiple sclerosis in the North East (Grampian Region) of Scotland – an update. J Epidemiol Community Health. 1987:41(1):5–13. https://doi.org/10.1136/jech.4....
 
44.
Ford HL, Gerry E, Airey CM, Vail A, Johnson MH, Williams DR. The prevalence of multiple sclerosis in the Leeds Health Authority. J Neurol Neurosurg Psychiatry. 1998:64(5):605–610. https://doi.org/10.1136/jnnp.6....
 
45.
Shepherd DI, Summers A. Prevalence of multiple sclerosis in Rochdale. J Neurol Neurosurg Psychiatry. 1996:61(4):415–417. https://doi.org/10.1136/jnnp.6....
 
46.
Robertson NP, Deans J, Fraser M, Compston DAS. Multiple sclerosis in the North Cambridgeshire districts of East Anglia. J Neurol Neurosurg Psychiatry. 1995;59:71–76. https://doi.org/10.1136/jnnp.5....
 
47.
Mumford CJ, Fraser MB, Wood NW, Compston DAS. Multiple sclerosis in the Cambridge health district of East Anglia. J Neurol Neurosurg Psychiatry. 1992;55:877–882. https://doi.org/10.1136/jnnp.5....
 
48.
Williams ES, McKeran RO. Prevalence of multiple sclerosis in a South London borough. British Med J. 1986;293(6541):237–239. https://doi.org/10.1136/bmj.29....
 
49.
Swingler RJ, Compston DAS. Demographic characteristics of multiple sclerosis in south East Wales. Neuroepidemiology. 1990;9:68–77. https://doi.org/10.1159/000110....
 
50.
Rice-Oxley M, Rees JR, Williams ES. A prevalent survey of multiple sclerosis in Sussex. J Neurol Neurosurg Psychiatry. 1995;58:27–30. https://doi.org/10.1136/jnnp.5....
 
51.
Roberts MHV, Martin GP, McLelland DL, McIntosh-Michaelis SA, Spackman AJ. The prevalence of multiple sclerosis in the Southampton South West Hampshire Health Authority. J Neurol Neurosurg Psychiatry. 1991;54(1):55–59. https://doi.org/10.1136/jnnp.5....
 
52.
Sharpe G, Price SE, Last A, Thompson RJ. Multiple sclerosis in island population: prevalence in the Bailiwicks of Guernsey and Jersey. J Neurol Neurosurg Psychiatry. 1995;58(1):22–26. https://doi.org/10.1136/jnnp.5....
 
53.
McDonnel GV, Hawkins SA. An epidemiologic study of multiple sclerosis in Northern Ireland. Neurology. 1998;50(2):423–428. https://doi.org/10.1212/WNL.50....
 
54.
Forbes RB, Wilson SV, Swingler RJ. The prevalence of multiple sclerosis in Tayside, Scotland: do latitudinal gradients really exist? J Neurol. 1999;246(11):1033–1040. https://doi.org/10.1007/s00415....
 
55.
Rothwell PM, Charlton D. High incidence and prevalence of multiple sclerosis in South East Scotland: evidence of a genetic predisposition. J Neurol Neurosurg Psychiatry. 1998;64(6):730–735. https://doi.org/10.1136/jnnp.6....
 
56.
Cook SD, Cromarty MB, Tapp W, Poskanzer D, Walker JD, Dowling PC. Declining incidence of multiple sclerosis in the Orkney Islands. Neurology. 1985;35(4):545–551. https://doi.org/10.1212/WNL.35....
 
57.
Poskanzer DC, Prenney LP, Sheridan JL, Yon Kondy J. Multiple sclerosis in the Orkney and Shetland Islands. I. Epidemiology, clinical factors, and methodology. J Epidemiol Community Health. 1980;34(4):229–239. https://doi.org/10.1136/jech.3....
 
58.
Materljan E, Sepcic J. Multiple sclerosis in Croatia. In: Firnhaber W, Lauer K, eds. Multiple Sclerosis in Europe: An Epidemiological Update. Darmstadt: Leuchtturm. 1994:295–300.
 
59.
Materljan E, Sepcic J, Antonelli L. Multiple sclerosis in Istria, Yugoslavia. Neurologija. 1989;38(3):201–212.
 
60.
Poljakovic Z, Franjic J. Incidencija multiple skleroze na uzem podrucju grada Zagreba. In: Nikolic M, ed. Neuroloska istrazivanja. Prvi jugoslavenski simpozijum o multiploj sklerozi. Galenika Beograd: Donji Milanovac. 1980;20–23.
 
61.
Sepcic J, Materljan E, Antonelli L, Sepcic-Grahovac D. Multiple sclerosis cluster in Gorski Kotar, Croatia,Yugoslavia. In: Battaglia MA, ed. Multiple Sclerosis Research. Amsterdam: Elsevier. 1989:165–169.
 
62.
Odorcic L. Distribution of multiple sclerosis in the municipalities of Kocevje and Ribnica [graduation thesis]. University of Zagreb, Croatia. 1987.
 
63.
Levic Z, Pantovic M, Sepcic J. Epidemiologic studies of multiple sclerosis in Yugoslavia. Neurologija. 1984;34:89–96.
 
64.
Verdes F, Petrescu A, Cernescu M. Epidemiology survey of multiple sclerosis in Bucharest city and suburban area. Acta Neurol Scand. 1979;58:109–120. https://doi.org/10.1111/j.1600....
 
65.
Georgiev D, Milanov I, Tzonev V, Kalafatova O. The epidemiology of multiple sclerosis in Sofia. In: Firnhaber W, Lauer K, eds. Multiple Sclerosis in Europe: An Epidemiological Update. Darmstadt: Leuchtturm. 1994;322–325.
 
66.
Milanov I, Georgiev D, Kmetska K, Jordanova L, Topalov N. Prevalence of multiple sclerosis in Bulgaria. Neuroepidemiology. 1997;16:304–307. https://doi.org/10.1159/000109....
 
67.
Milanov I, Topalov N, Kmetski TS. Prevalence of multiple sclerosis in Gypsies and Bulgarians. Neuroepidemiology. 1999;18(4):218–222. https://doi.org/10.1159/000026....
 
68.
Topalov N, Chalmanov V, Tzonev V. The prevalence of multiple sclerosis in the region of Samokov and Pavlikeny, Bulgaria. Mult Scler. 1998:4:368.
 
69.
Ljapchev R, Daskalovska V. Epidemiological studies of multiple sclerosis in the Republic of Macedonia. In: Firnhaber W, Lauer K, eds. Multiple Sclerosis in Europe: An Epidemiological Update. Darmstadt: Leuchtturm. 1994;301–308.